2. Academic Validation
  3. Rapid quantification of vincristine in mouse plasma using ESI-LC-MS/MS: Application to pharmacokinetic studies

Rapid quantification of vincristine in mouse plasma using ESI-LC-MS/MS: Application to pharmacokinetic studies

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Apr 1:1168:122591. doi: 10.1016/j.jchromb.2021.122591.
Yan Jin 1,  Yang Li 1,  Muhammad Erfan Uddin 1,  Alex Sparreboom 1,  Shuiying Hu 2
Affiliations

Affiliations

  • 1 Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
  • 2 Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA. Electronic address: [email protected].
PMID: 33684722 DOI: 10.1016/j.jchromb.2021.122591
Abstract

A simple, rapid, and sensitive LC-MS/MS method for determining concentrations of the Anticancer alkaloid vincristine in micro volumes of mouse plasma was developed and validated in positive ion mode. Separation of vincristine and the internal standard [2H3]-vincristine was achieved on an Accucore aQ column with a gradient mobile phase delivered at a flow rate of 0.4 mL/min and a run time of 2.2 min. Calibration curves were linear (r2 > 0.99, n = 8) up to 250 ng/mL, with a lower limit of quantitation of 2.5 ng/mL. The matrix effect and extraction recovery for vincristine were ranging 108-110% and 88.4-107%, respectively. The intra-day and inter-day precision of quality controls tested at 3 different concentrations were always less than 15%, and accuracy ranged from 91.7 to 107%. The method was successfully applied to evaluate the pharmacokinetic profile of vincristine in wild-type and CYP3A-deficient mice in support of a project to provide mechanistic insight into drug-drug interactions and to identify sources of inter-individual pharmacokinetic variability associated with vincristine-induced peripheral neuropathy.

Keywords

Mouse plasma; Pharmacokinetics; UHPLC-MS/MS; Vincristine.

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