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Method development and validation of capillary sodium dodecyl sulfate gel electrophoresis for the characterization of a monoclonal antibody
Journal article   Peer reviewed

Method development and validation of capillary sodium dodecyl sulfate gel electrophoresis for the characterization of a monoclonal antibody

Junge Zhang, Sudhir Burman, Sri Gunturi and Joe P Foley
Journal of pharmaceutical and biomedical analysis, v 53(5), pp 1236-1243
2010
PMID: 20719453

Abstract

CGE cSDS IgG purity Monoclonal antibody
A capillary sodium dodecyl sulfate gel electrophoresis (cSDS) method has been developed and qualified for purity and impurity analysis of monoclonal antibodies. This method was optimized and qualified for the analysis of monoclonal antibody (mAb1) under reduced and non-reduced conditions. Some of the sample preparation parameters including sample buffer pH, incubation temperature and duration, alkylation conditions with iodoacetamide (IAM), and reduction conditions with 2-mercaptoethanol (2-ME) were optimized. It was observed that under slightly acidic conditions (pH 5.5–6.5) the thermally induced fragmentation of non-reduced mAb1 was greatly decreased. As such, a citrate–phosphate buffer at pH 6.5 was used for sample preparation to replace the original Beckman sample buffer (pH 9.0). The optimal sample preparation conditions were found to be as follows: (1) incubation temperature and duration (reduced and non-reduced), 65 °C for 5 min; (2) alkylation condition, 10 μL of 0.25 M IAM; (3) reduction condition, 10 μL of 5-fold diluted 2-ME. The method was qualified by evaluating specificity, accuracy, precision, limit of quantitation (LOQ), and linearity. The method exhibited no interference from sample buffer matrix. The method was found to be linear, accurate, and precise in the range of 0.25–3.0 mg/mL protein concentration. The LOQ of the method was determined to be 0.02 mg/mL for reduced and non-reduced mAb1. In addition, some aspects of sample stability were examined during qualification.

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Chemistry, Analytical
Pharmacology & Pharmacy
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