Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development

Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Lin, Ziqing [verfasserIn] Wang, Qinggang [verfasserIn] Zhou, Yiyang [verfasserIn] Shackman, Jonathan G. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification

Übergeordnetes Werk:	Enthalten in: Journal of chromatography / A - New York, NY [u.a.] : Science Direct, 1958, 1700
Übergeordnetes Werk:	volume:1700

DOI / URN:	10.1016/j.chroma.2023.464043

Katalog-ID:	ELV00974987X

Internformat


LEADER	01000caa a22002652 4500
001	ELV00974987X
003	DE-627
005	20231205153927.0
007	cr uuu---uuuuu
008	230530s2023 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1016/j.chroma.2023.464043 \|2 doi
035			\|a (DE-627)ELV00974987X
035			\|a (ELSEVIER)S0021-9673(23)00269-8
040			\|a DE-627 \|b ger \|c DE-627 \|e rda
041			\|a eng
082	0	4	\|a 540 \|q VZ
084			\|a 35.00 \|2 bkl
100	1		\|a Lin, Ziqing \|e verfasserin \|0 (orcid)0000-0003-0464-5263 \|4 aut
245	1	0	\|a Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development
264		1	\|c 2023
336			\|a nicht spezifiziert \|b zzz \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories.
650		4	\|a 2D-LC
650		4	\|a Trapping mode
650		4	\|a Low-level impurity
650		4	\|a Pharmaceutical
650		4	\|a Quantification
700	1		\|a Wang, Qinggang \|e verfasserin \|4 aut
700	1		\|a Zhou, Yiyang \|e verfasserin \|0 (orcid)0000-0002-9165-6042 \|4 aut
700	1		\|a Shackman, Jonathan G. \|e verfasserin \|4 aut
773	0	8	\|i Enthalten in \|t Journal of chromatography / A \|d New York, NY [u.a.] : Science Direct, 1958 \|g 1700 \|h Online-Ressource \|w (DE-627)302467416 \|w (DE-600)1491247-8 \|w (DE-576)094950253 \|x 1873-3778 \|7 nnns
773	1	8	\|g volume:1700
912			\|a GBV_USEFLAG_U
912			\|a GBV_ELV
912			\|a SYSFLAG_U
912			\|a SSG-OLC-PHA
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_32
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_90
912			\|a GBV_ILN_95
912			\|a GBV_ILN_100
912			\|a GBV_ILN_101
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2007
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2088
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2122
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2143
912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2470
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
912			\|a GBV_ILN_4700
936	b	k	\|a 35.00 \|j Chemie: Allgemeines \|q VZ
951			\|a AR
952			\|d 1700

Indexfelder

author_variant	z l zl q w qw y z yz j g s jg jgs
matchkey_str	article:18733778:2023----::rpigoewdmninliudhoaorpyoqatttvlweeiprtercm
hierarchy_sort_str	2023
bklnumber	35.00
publishDate	2023
allfields	10.1016/j.chroma.2023.464043 doi (DE-627)ELV00974987X (ELSEVIER)S0021-9673(23)00269-8 DE-627 ger DE-627 rda eng 540 VZ 35.00 bkl Lin, Ziqing verfasserin (orcid)0000-0003-0464-5263 aut Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories. 2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification Wang, Qinggang verfasserin aut Zhou, Yiyang verfasserin (orcid)0000-0002-9165-6042 aut Shackman, Jonathan G. verfasserin aut Enthalten in Journal of chromatography / A New York, NY [u.a.] : Science Direct, 1958 1700 Online-Ressource (DE-627)302467416 (DE-600)1491247-8 (DE-576)094950253 1873-3778 nnns volume:1700 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.00 Chemie: Allgemeines VZ AR 1700
spelling	10.1016/j.chroma.2023.464043 doi (DE-627)ELV00974987X (ELSEVIER)S0021-9673(23)00269-8 DE-627 ger DE-627 rda eng 540 VZ 35.00 bkl Lin, Ziqing verfasserin (orcid)0000-0003-0464-5263 aut Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories. 2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification Wang, Qinggang verfasserin aut Zhou, Yiyang verfasserin (orcid)0000-0002-9165-6042 aut Shackman, Jonathan G. verfasserin aut Enthalten in Journal of chromatography / A New York, NY [u.a.] : Science Direct, 1958 1700 Online-Ressource (DE-627)302467416 (DE-600)1491247-8 (DE-576)094950253 1873-3778 nnns volume:1700 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.00 Chemie: Allgemeines VZ AR 1700
allfields_unstemmed	10.1016/j.chroma.2023.464043 doi (DE-627)ELV00974987X (ELSEVIER)S0021-9673(23)00269-8 DE-627 ger DE-627 rda eng 540 VZ 35.00 bkl Lin, Ziqing verfasserin (orcid)0000-0003-0464-5263 aut Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories. 2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification Wang, Qinggang verfasserin aut Zhou, Yiyang verfasserin (orcid)0000-0002-9165-6042 aut Shackman, Jonathan G. verfasserin aut Enthalten in Journal of chromatography / A New York, NY [u.a.] : Science Direct, 1958 1700 Online-Ressource (DE-627)302467416 (DE-600)1491247-8 (DE-576)094950253 1873-3778 nnns volume:1700 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.00 Chemie: Allgemeines VZ AR 1700
allfieldsGer	10.1016/j.chroma.2023.464043 doi (DE-627)ELV00974987X (ELSEVIER)S0021-9673(23)00269-8 DE-627 ger DE-627 rda eng 540 VZ 35.00 bkl Lin, Ziqing verfasserin (orcid)0000-0003-0464-5263 aut Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories. 2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification Wang, Qinggang verfasserin aut Zhou, Yiyang verfasserin (orcid)0000-0002-9165-6042 aut Shackman, Jonathan G. verfasserin aut Enthalten in Journal of chromatography / A New York, NY [u.a.] : Science Direct, 1958 1700 Online-Ressource (DE-627)302467416 (DE-600)1491247-8 (DE-576)094950253 1873-3778 nnns volume:1700 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.00 Chemie: Allgemeines VZ AR 1700
allfieldsSound	10.1016/j.chroma.2023.464043 doi (DE-627)ELV00974987X (ELSEVIER)S0021-9673(23)00269-8 DE-627 ger DE-627 rda eng 540 VZ 35.00 bkl Lin, Ziqing verfasserin (orcid)0000-0003-0464-5263 aut Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories. 2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification Wang, Qinggang verfasserin aut Zhou, Yiyang verfasserin (orcid)0000-0002-9165-6042 aut Shackman, Jonathan G. verfasserin aut Enthalten in Journal of chromatography / A New York, NY [u.a.] : Science Direct, 1958 1700 Online-Ressource (DE-627)302467416 (DE-600)1491247-8 (DE-576)094950253 1873-3778 nnns volume:1700 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.00 Chemie: Allgemeines VZ AR 1700
language	English
source	Enthalten in Journal of chromatography / A 1700 volume:1700
sourceStr	Enthalten in Journal of chromatography / A 1700 volume:1700
format_phy_str_mv	Article
bklname	Chemie: Allgemeines
institution	findex.gbv.de
topic_facet	2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification
dewey-raw	540
isfreeaccess_bool	false
container_title	Journal of chromatography / A
authorswithroles_txt_mv	Lin, Ziqing @@aut@@ Wang, Qinggang @@aut@@ Zhou, Yiyang @@aut@@ Shackman, Jonathan G. @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	302467416
dewey-sort	3540
id	ELV00974987X
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV00974987X</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20231205153927.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230530s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.chroma.2023.464043</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV00974987X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0021-9673(23)00269-8</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">540</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">35.00</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Lin, Ziqing</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-0464-5263</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">2D-LC</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Trapping mode</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Low-level impurity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pharmaceutical</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Quantification</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Qinggang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhou, Yiyang</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-9165-6042</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Shackman, Jonathan G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Journal of chromatography / A</subfield><subfield code="d">New York, NY [u.a.] : Science Direct, 1958</subfield><subfield code="g">1700</subfield><subfield code="h">Online-Ressource</subfield><subfield code="w">(DE-627)302467416</subfield><subfield code="w">(DE-600)1491247-8</subfield><subfield code="w">(DE-576)094950253</subfield><subfield code="x">1873-3778</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:1700</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_150</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_187</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2001</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2007</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2008</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2010</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2015</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2020</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2021</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2025</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2026</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2027</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2044</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2048</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2049</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2050</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2056</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2059</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2061</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2064</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2088</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2106</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2122</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2129</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2143</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2190</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2232</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2470</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2507</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4035</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4242</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4333</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4334</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4393</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">35.00</subfield><subfield code="j">Chemie: Allgemeines</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">1700</subfield></datafield></record></collection>
author	Lin, Ziqing
spellingShingle	Lin, Ziqing ddc 540 bkl 35.00 misc 2D-LC misc Trapping mode misc Low-level impurity misc Pharmaceutical misc Quantification Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development
authorStr	Lin, Ziqing
ppnlink_with_tag_str_mv	@@773@@(DE-627)302467416
format	electronic Article
dewey-ones	540 - Chemistry & allied sciences
delete_txt_mv	keep
author_role	aut aut aut aut
collection	elsevier
remote_str	true
illustrated	Not Illustrated
issn	1873-3778
topic_title	540 VZ 35.00 bkl Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development 2D-LC Trapping mode Low-level impurity Pharmaceutical Quantification
topic	ddc 540 bkl 35.00 misc 2D-LC misc Trapping mode misc Low-level impurity misc Pharmaceutical misc Quantification
topic_unstemmed	ddc 540 bkl 35.00 misc 2D-LC misc Trapping mode misc Low-level impurity misc Pharmaceutical misc Quantification
topic_browse	ddc 540 bkl 35.00 misc 2D-LC misc Trapping mode misc Low-level impurity misc Pharmaceutical misc Quantification
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	Journal of chromatography / A
hierarchy_parent_id	302467416
dewey-tens	540 - Chemistry
hierarchy_top_title	Journal of chromatography / A
isfreeaccess_txt	false
familylinks_str_mv	(DE-627)302467416 (DE-600)1491247-8 (DE-576)094950253
title	Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development
ctrlnum	(DE-627)ELV00974987X (ELSEVIER)S0021-9673(23)00269-8
title_full	Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development
author_sort	Lin, Ziqing
journal	Journal of chromatography / A
journalStr	Journal of chromatography / A
lang_code	eng
isOA_bool	false
dewey-hundreds	500 - Science
recordtype	marc
publishDateSort	2023
contenttype_str_mv	zzz
author_browse	Lin, Ziqing Wang, Qinggang Zhou, Yiyang Shackman, Jonathan G.
container_volume	1700
class	540 VZ 35.00 bkl
format_se	Elektronische Aufsätze
author-letter	Lin, Ziqing
doi_str_mv	10.1016/j.chroma.2023.464043
normlink	(ORCID)0000-0003-0464-5263 (ORCID)0000-0002-9165-6042
normlink_prefix_str_mv	(orcid)0000-0003-0464-5263 (orcid)0000-0002-9165-6042
dewey-full	540
author2-role	verfasserin
title_sort	trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development
title_auth	Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development
abstract	Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories.
abstractGer	Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories.
abstract_unstemmed	Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories.
collection_details	GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700
title_short	Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development
remote_bool	true
author2	Wang, Qinggang Zhou, Yiyang Shackman, Jonathan G.
author2Str	Wang, Qinggang Zhou, Yiyang Shackman, Jonathan G.
ppnlink	302467416
mediatype_str_mv	c
isOA_txt	false
hochschulschrift_bool	false
doi_str	10.1016/j.chroma.2023.464043
up_date	2024-07-07T00:13:21.874Z
_version_	1803877038819377152
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV00974987X</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20231205153927.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230530s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.chroma.2023.464043</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV00974987X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0021-9673(23)00269-8</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">540</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">35.00</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Lin, Ziqing</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-0464-5263</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">2D-LC</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Trapping mode</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Low-level impurity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pharmaceutical</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Quantification</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Qinggang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhou, Yiyang</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-9165-6042</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Shackman, Jonathan G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Journal of chromatography / A</subfield><subfield code="d">New York, NY [u.a.] : Science Direct, 1958</subfield><subfield code="g">1700</subfield><subfield code="h">Online-Ressource</subfield><subfield code="w">(DE-627)302467416</subfield><subfield code="w">(DE-600)1491247-8</subfield><subfield code="w">(DE-576)094950253</subfield><subfield code="x">1873-3778</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:1700</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_150</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_187</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2001</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2007</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2008</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2010</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2015</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2020</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2021</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2025</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2026</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2027</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2044</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2048</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2049</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2050</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2056</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2059</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2061</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2064</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2088</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2106</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2122</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2129</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2143</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2190</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2232</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2470</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2507</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4035</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4242</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4333</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4334</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4393</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">35.00</subfield><subfield code="j">Chemie: Allgemeines</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">1700</subfield></datafield></record></collection>
score	7.401043

Nicht das Richtige dabei?

Schreiben Sie uns!

Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?