title: Simultaneous analysis of multiple monoclonal antibody biotherapeutics by LC-MS/MS method in rat plasma following cassette-dosing.
abstract: We have recently developed a general liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using a stable isotope-labeled (SIL) monoclonal antibody (mAb) as an internal standard (IS) for single-analyte quantification of mAb (Li et al. Anal Chem 84(3):1267-1273, 2012). The method offers an advantage over ligand binding assay in reducing the time and resources needed for bioanalytical support in preclinical stages of drug development. In this paper, we report another marked increase in assay efficiency for multi-analyte bioanalysis using unique surrogate peptides for each analyte and the strategic choice of the SIL-IS peptide. The method was qualified for the simultaneous determinations of four mAbs in rat plasma and applied to samples from discrete- and cassette-dosed rats. The pharmacokinetic parameters of the four mAbs of cassette dosing were comparable to those of discrete dosing and of enzyme-linked immunosorbent assay results. Although there may be limitations and special considerations for cassette-dosing of biologics, these results demonstrate the robust performance of the multi-analyte LC-MS/MS method allowing cassette-dosing that would ultimately reduce animal use and improve efficiency.
authors.affiliation: Departments of PKDM, Amgen Inc, One Amgen Center Drive, Mail Stop 30E-3-B, Thousand Oaks, CA 91320, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Ortiz
authors.forename: Linh T B
authors.initials: LT
authors.lastname: Tran
authors.forename: Hossein
authors.initials: H
authors.lastname: Salimi-Moosavi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Malella
authors.forename: Christopher A
authors.initials: CA
authors.lastname: James
authors.forename: Jean W
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001688:Biological Products / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001711:Biotransformation; D002138:Calibration; D002853:Chromatography, Liquid / Q000592:standards; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D007279:Injections, Subcutaneous; D010446:Peptide Fragments / Q000097:blood; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products; D004338:Drug Combinations; D010446:Peptide Fragments