title: Sensitive and specific LC-ESI-MS/MS method for determination of ZYDPLA1, a novel long-acting dipeptidyl peptidase 4 inhibitor in rat plasma: An application for toxicokinetic study in rats.
abstract: A rapid and highly specific assay was developed and validated for the estimation of ZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as specificity, matrix effect, precision, accuracy, recovery, stability, etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising: (A) 0.2% ammonia in purified water; (B) 0.1% formic acid in isopropyl alcohol/methanol (1: 1 v/v); and (C) acetonitrile at a flow rate of 1 mL/min on an ACE-5, C18 (4.6 × 50 mm) column with a run time of 5.5 min. The quantitation of ZYDPLA1 was achieved by the summation of four multiple reaction mode transitions (m/z 399.7 → 383.0, 399.7 → 276.10, 399.7 → 153.20 and 399.7 → 127.20), while that of the internal standard was by a single multiple reaction mode transition (m/z 309.10 → 281.00). The lower limit of quantitation achieved was 0.01 μg/mL and the method showed linearity from 0.01 to 25 μg/mL. The intra- and inter-day precision (%CV) of the quality control samples was within 8.81% and accuracy was ±10% of nominal values. This novel method was applied for evaluation of toxicokinetics of ZYDLA1 in rats.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Giri
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Bharat
authors.initials: B
authors.lastname: Patel
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Harilal
authors.initials: H
authors.lastname: Patel
authors.affiliation: Department of Medicinal Chemistry, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bahekar
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Nuggehally R
authors.identifier: http://orcid.org/0000-0002-5768-1332
authors.initials: NR
authors.lastname: Srinivas
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.|Department of Medicinal Chemistry, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Pankaj R
authors.initials: PR
authors.lastname: Patel
authors.affiliation: Department of Medicinal Chemistry, Zydus Research Centre, A Division of Cadila Healthcare Ltd., Ahmedabad, India.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Desai
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors
keywords: DPP-4 inhibitor; LC-ESI-MS/MS; Toxicokinetics; ZYDPLA1; method validations; rat plasmasss