A sensitive liquid chromatography–mass spectrometry bioanalytical assay for a novel anticancer candidate – ZMC1. (5th May 2015)

• Record Type: Journal Article
• Authors: Lin, Hongxia; Yu, Xin; Eng, Oliver S.; Buckley, Brian; Kong, Ah‐Ng Tony; Bertino, Joseph R.; Carpizo, Darren R.; Gounder, Murugesan K.
• Is Part Of: Biomedical chromatography. Volume 29:Number 11(2015:Nov.)
• Page Start: 1708
• Page End: 1714
• Publication Date: 2015-05-05
• Subjects: Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.3483
• Languages: English
• ISSNs: 0269-3879

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>ZMC1 {azetidinecarbothioic acid, [1‐(2‐pyridinyl) ethylidene] hydrazide} is a lead compound being developed as one of the first mutant p53 targeted anti‐cancer drugs. Establishing a precise quantitative method is an integral component of this development. The aim of this study was to develop a sensitive LC/MS/MS assay suitable for assessing purity, stability and preclinical pharmacokinetic studies of ZMC1. Acetonitrile protein precipitation extraction was chosen for plasma sample preparation with satisfactory recovery (84.2–92.8%) for ZMC1. Chromatographic separation was achieved on an Xterra C<sub>18</sub> column (50 × 4.6 mm, 3.5 µm) using a gradient elution with mobile phase of 0.1% formic acid in water and acetonitrile. ZMC1 and internal standard 2‐amino‐6‐bromobenzothiazole were identified using selected‐ion monitoring mode at <italic>m</italic>/<italic>z</italic> 235.2/178.2 and <italic>m</italic>/<italic>z</italic> 231.0/150.0 at retention times of 5.2 and 6.3 min, respectively. The method was validated with a linearity range of 3.9–500.0 ng/mL in human plasma and showed acceptable reproducibility with intra‐ and interday precisions <5.9 and 10.5%, and accuracy within ±5.4% of nominal values. This analytical method together with basic stability data in plasma and plasma binding experiments provides a reliable protocol for the study of ZMC1 pharmacokinetics. This will greatly facilitate the pre‐clinical development of this novel anti‐cancer drug. Copyright © 2015 John Wiley & Sons, Ltd.</p> </abstract>