LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics
AbstractQuantitative targeted proteomics based approaches deploy state-of-the-art Liquid chromatography tandem mass spectrometry LC-MS technologies and are evolving as a complementary technique to standard ligand-binding based assays. Advancements in MS technology, which have augmented the specificity, selectivity and sensitivity limits of detection and freedom from antibody generation, have made it amicable towards various clinical applications. In our current work, a surrogate peptide based quantitative proteomics assessment is performed by selecting specific signature peptides from the complementary determining region CDR region of trastuzumab (Herclon®, Roche products in India). We developed a double Stable Isotope Label (dSIL) approach by using two different surrogate peptides to evaluate the proteolytic digestion efficiency and accurate quantification of the target analyte peptide of Herclon® in human serum. Method validation experiments were meticulously performed as per bioanalytical method validation guidelines. The dSIL approach, using an LC-MS/MS based quantification assay demonstrated good linearity over a range of 5–500 µg/mL of Herclon®, and validation experimental data is in compliance with bioanalytical regulatory guidelines. View Full-Text
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Budhraja, R.H.; Shah, M.A.; Suthar, M.; Yadav, A.; Shah, S.P.; Kale, P.; Asvadi, P.; Valan Arasu, M.; Al-Dhabi, N.A.; Park, C.G.; Kim, Y.-O.; Kim, H.J.; Agrawal, Y.K.; Krovidi, R.K. LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics. Molecules 2016, 21, 1464.
Budhraja RH, Shah MA, Suthar M, Yadav A, Shah SP, Kale P, Asvadi P, Valan Arasu M, Al-Dhabi NA, Park CG, Kim Y-O, Kim HJ, Agrawal YK, Krovidi RK. LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics. Molecules. 2016; 21(11):1464.Chicago/Turabian Style
Budhraja, Rohit H.; Shah, Milin A.; Suthar, Mahendra; Yadav, Arun; Shah, Sahil P.; Kale, Prashant; Asvadi, Parisa; Valan Arasu, Mariadhas; Al-Dhabi, Naif A.; Park, Chun G.; Kim, Young-Ock; Kim, Hak J.; Agrawal, Y. K.; Krovidi, Ravi. K. 2016. "LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics." Molecules 21, no. 11: 1464.
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