LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics.
Quantitative 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.
Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India. rohitbudhraja@gmail.com.
Rohit H
RH
Budhraja
Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India. milinshah@lambda-cro.com.
Milin A
MA
Shah
Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India. mahendramevada8@gmail.com.
Mahendra
M
Suthar
Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India. arunyadavpoo@gmail.com.
Arun
A
Yadav
Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India. sahilshah.ind@gmail.com.
Sahil P
SP
Shah
Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India. prashant@lambda-cro.com.|Department of Pharmaceutical Sciences, Gujarat Forensic Sciences University, Gandhinagar 382481, India. prashant@lambda-cro.com.
Prashant
P
Kale
Analytical Development and Global Regulatory Affairs, Intas Pharmaceuticals Ltd., Ahmedabad, Gujarat 382213, India. parisa_asvadi@intaspharma.com.
Parisa
P
Asvadi
Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. mvalanarasu@gmail.com.
Mariadhas
M
Valan Arasu
Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. naldhabi@ksu.edu.sa.
Naif Abdullah
NA
Al-Dhabi
Department of Medicinal Crop Research, Rural Development Administration, Eumseong, Chungbuk 369-873, Korea. pcg@korea.kr.
Chun Geon
CG
Park
Department of Medicinal Crop Research, Rural Development Administration, Eumseong, Chungbuk 369-873, Korea. kyo9128@korea.kr.
Young-Ock
YO
Kim
Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea. hak3962@sch.ac.kr.
Hak Jae
HJ
Kim
Department of Pharmaceutical Sciences, Gujarat Forensic Sciences University, Gandhinagar 382481, India. drykagrawal@yahoo.com.
Y K
YK
Agrawal
Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India. ravikrovidi@gmail.com.
Ravi K
RK
Krovidi
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D006801:Humans; D007553:Isotope Labeling; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D000068878:Trastuzumab / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D010455:Peptides; D000068878:Trastuzumab
LC-MS/MS; dSIL; pharmacokinetics; trastuzumab