Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 223, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jpba.2022.115163
Keywords
Emicizumab; Mass spectrometry; Pharmacokinetic; Therapeutic drug monitoring
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This study developed a method for absolute quantification of emicizumab using LC-MS/MS, which was validated according to FDA recommendations and showed good correlation with the traditional FVIII activity assay.
Emicizumab is a new therapeutic monoclonal antibody indicated for prophylaxis in severe haemophilia A pa-tients. Pharmacokinetic variability has been reported in clinical studies, thus dose optimisation based on quantification of plasma drug concentration could be considered to reduce this variability. Therefore, a reliable and accurate quantification of emicizumab is required. In this study, we developed a method for absolute quantification of emicizumab using liquid chromatography coupled to triple quadrupole mass spectrometry (LC-MS/MS). Sample preparation was based on organic solvent precipitation of proteins followed by trypsin diges-tion. A signature peptide of emicizumab was used for quantification by LC-MS/MS. A stable isotope-labelled peptide was used as an internal standard. Finally, 6 samples from patients treated with emicizumab were quantified by LC-MS/MS and compared with those obtained with the modified one-stage activated partial pro -thrombin time technique (aPTT) based FVIII activity. The LC-MS/MS method was validated according to FDA recommendations. Good linearity of the calibration curves was observed over the range 5-150 mu g/mL. The cross -validation showed an acceptable correlation of the developed LC-MS/MS method with the modified aPTT-based FVIII activity assay, and the Bland-Altman analysis did not show any significant bias.
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