Liquid chromatography-mass spectrometry for quantification of the anti-chemotherapeutic antibody in rat plasma / 国际药学研究杂志

ABSTRACT

Objective To establish a sensitive,accurate and reliable LC-MS method to quantify the monoclonal antibody in rat blood and preclinical pharmacokinetics study. Methods The method of selective reaction monitoring(SRM)was established by using on-the-fly orthogonal array optimization(OAO)with anti-chemotherapeutic antibody-06(ACA-06)as a model drug,and the pharmacokinetics of ACA-06 in rats was studied. The optimal signature peptide selection and mass spectrometry conditions were opti?mized by single LC-MS run. Two highly specific and sensitive peptides,FSGVPDR and VNSAAFPAPIEK,were identified as the sig?nature peptides of quantification based on the OAO optimization result,which were located in the ACA-06 light chain and heavy chain complementary determining region(CDR)respectively. Results The method had good linearity in the range of 12.9~32250 ng/ml (r20.9819-0.9946). The lower limit of quantification was 12.9 ng/ml. The intra-day precision(RSD)was less than 11.5%,the inter-day RSD was less than 6%,and the accuracy was between-4.0%and 4.3%. Conclusion In this study,LC/SRM-MS method is es?tablished for the determination of ACA-06 in rat plasma. The method is specific,accurate and sensitive and enables an accurate phar?macokinetics investigation of ACA-06 in rat plasma.