High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products
Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in orde...
Ausführliche Beschreibung
Autor*in: |
Hebbi, Vishwanath [verfasserIn] Chattopadhyay, Soumili [verfasserIn] Rathore, Anurag S. [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: Journal of chromatography / B - New York, NY [u.a.] : Science Direct, 1977, 1117, Seite 118-126 |
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Übergeordnetes Werk: |
volume:1117 ; pages:118-126 |
DOI / URN: |
10.1016/j.jchromb.2019.04.022 |
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Katalog-ID: |
ELV002156415 |
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520 | |a Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. | ||
650 | 4 | |a Excipient | |
650 | 4 | |a Ion exclusion chromatography | |
650 | 4 | |a Ion pairing chromatography | |
650 | 4 | |a Monoclonal antibodies | |
700 | 1 | |a Chattopadhyay, Soumili |e verfasserin |4 aut | |
700 | 1 | |a Rathore, Anurag S. |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Journal of chromatography / B |d New York, NY [u.a.] : Science Direct, 1977 |g 1117, Seite 118-126 |h Online-Ressource |w (DE-627)302467505 |w (DE-600)1491259-4 |w (DE-576)094950261 |x 1873-376X |7 nnns |
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912 | |a GBV_ILN_4335 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4393 | ||
936 | b | k | |a 35.29 |j Chromatographische Analyse |j Elektrophorese |
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2019 |
allfields |
10.1016/j.jchromb.2019.04.022 doi (DE-627)ELV002156415 (ELSEVIER)S1570-0232(19)30241-7 DE-627 ger DE-627 rda eng 540 DE-600 35.29 bkl 44.46 bkl Hebbi, Vishwanath verfasserin aut High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. Excipient Ion exclusion chromatography Ion pairing chromatography Monoclonal antibodies Chattopadhyay, Soumili verfasserin aut Rathore, Anurag S. verfasserin aut Enthalten in Journal of chromatography / B New York, NY [u.a.] : Science Direct, 1977 1117, Seite 118-126 Online-Ressource (DE-627)302467505 (DE-600)1491259-4 (DE-576)094950261 1873-376X nnns volume:1117 pages:118-126 GBV_USEFLAG_U SYSFLAG_U GBV_ELV 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_63 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_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.29 Chromatographische Analyse Elektrophorese 44.46 Klinische Pathologie AR 1117 118-126 |
spelling |
10.1016/j.jchromb.2019.04.022 doi (DE-627)ELV002156415 (ELSEVIER)S1570-0232(19)30241-7 DE-627 ger DE-627 rda eng 540 DE-600 35.29 bkl 44.46 bkl Hebbi, Vishwanath verfasserin aut High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. Excipient Ion exclusion chromatography Ion pairing chromatography Monoclonal antibodies Chattopadhyay, Soumili verfasserin aut Rathore, Anurag S. verfasserin aut Enthalten in Journal of chromatography / B New York, NY [u.a.] : Science Direct, 1977 1117, Seite 118-126 Online-Ressource (DE-627)302467505 (DE-600)1491259-4 (DE-576)094950261 1873-376X nnns volume:1117 pages:118-126 GBV_USEFLAG_U SYSFLAG_U GBV_ELV 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_63 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_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.29 Chromatographische Analyse Elektrophorese 44.46 Klinische Pathologie AR 1117 118-126 |
allfields_unstemmed |
10.1016/j.jchromb.2019.04.022 doi (DE-627)ELV002156415 (ELSEVIER)S1570-0232(19)30241-7 DE-627 ger DE-627 rda eng 540 DE-600 35.29 bkl 44.46 bkl Hebbi, Vishwanath verfasserin aut High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. Excipient Ion exclusion chromatography Ion pairing chromatography Monoclonal antibodies Chattopadhyay, Soumili verfasserin aut Rathore, Anurag S. verfasserin aut Enthalten in Journal of chromatography / B New York, NY [u.a.] : Science Direct, 1977 1117, Seite 118-126 Online-Ressource (DE-627)302467505 (DE-600)1491259-4 (DE-576)094950261 1873-376X nnns volume:1117 pages:118-126 GBV_USEFLAG_U SYSFLAG_U GBV_ELV 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_63 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_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.29 Chromatographische Analyse Elektrophorese 44.46 Klinische Pathologie AR 1117 118-126 |
allfieldsGer |
10.1016/j.jchromb.2019.04.022 doi (DE-627)ELV002156415 (ELSEVIER)S1570-0232(19)30241-7 DE-627 ger DE-627 rda eng 540 DE-600 35.29 bkl 44.46 bkl Hebbi, Vishwanath verfasserin aut High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. Excipient Ion exclusion chromatography Ion pairing chromatography Monoclonal antibodies Chattopadhyay, Soumili verfasserin aut Rathore, Anurag S. verfasserin aut Enthalten in Journal of chromatography / B New York, NY [u.a.] : Science Direct, 1977 1117, Seite 118-126 Online-Ressource (DE-627)302467505 (DE-600)1491259-4 (DE-576)094950261 1873-376X nnns volume:1117 pages:118-126 GBV_USEFLAG_U SYSFLAG_U GBV_ELV 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_63 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_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.29 Chromatographische Analyse Elektrophorese 44.46 Klinische Pathologie AR 1117 118-126 |
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10.1016/j.jchromb.2019.04.022 doi (DE-627)ELV002156415 (ELSEVIER)S1570-0232(19)30241-7 DE-627 ger DE-627 rda eng 540 DE-600 35.29 bkl 44.46 bkl Hebbi, Vishwanath verfasserin aut High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. Excipient Ion exclusion chromatography Ion pairing chromatography Monoclonal antibodies Chattopadhyay, Soumili verfasserin aut Rathore, Anurag S. verfasserin aut Enthalten in Journal of chromatography / B New York, NY [u.a.] : Science Direct, 1977 1117, Seite 118-126 Online-Ressource (DE-627)302467505 (DE-600)1491259-4 (DE-576)094950261 1873-376X nnns volume:1117 pages:118-126 GBV_USEFLAG_U SYSFLAG_U GBV_ELV 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_63 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_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.29 Chromatographische Analyse Elektrophorese 44.46 Klinische Pathologie AR 1117 118-126 |
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540 DE-600 35.29 bkl 44.46 bkl High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products Excipient Ion exclusion chromatography Ion pairing chromatography Monoclonal antibodies |
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High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products |
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High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products |
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Hebbi, Vishwanath |
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Hebbi, Vishwanath Chattopadhyay, Soumili Rathore, Anurag S. |
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10.1016/j.jchromb.2019.04.022 |
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high performance liquid chromatography (hplc) based direct and simultaneous estimation of excipients in biopharmaceutical products |
title_auth |
High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products |
abstract |
Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. |
abstractGer |
Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. |
abstract_unstemmed |
Excipients are critical components of a biotherapeutic product as they have a direct impact on the product's stability and hence on its safety and efficacy. A typical biotherapeutic drug product has a variety of excipients and these need to be maintained within very tight specifications in order to ensure consistency in product quality. Hence, there is always a need for estimation of excipient concentration in the drug product. Deviations can occur during formulation process either due to inaccurate buffer preparation or during ultrafiltration/diafiltration of high protein concentration solutions. This paper reports on development of two high performance liquid chromatography (HPLC) based methods for direct and simultaneous estimation of excipients in biopharmaceutical products. Both the methods are modified such that protein is retained in the guard column resulted in clear separation of excipients without any baseline drifts. Ion exclusion chromatography (IEC) and ion pairing chromatography (IPC) have been successfully optimized for analysing 17 commonly used excipients. Operating conditions such as temperature, type of ion pairing agent, and mobile phase strength have been optimized. The proposed methods have been successfully validated as per regulatory guidelines with respect to linearity, accuracy, matrix interference, precision, limit of detection (LOD), and limit of quantification (LOQ). The methods have been successfully used for analysing excipients in a variety of biotherapeutics including insulin, granulocyte colony stimulating factor, rituximab, and ranibizumab. Further, utility of the proposed methods for process development has been demonstrated for designing an ultrafiltration/diafiltration process for one of the mAb products. |
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title_short |
High performance liquid chromatography (HPLC) based direct and simultaneous estimation of excipients in biopharmaceutical products |
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