title: Determination of S-propargyl-cysteine in rat plasma by mixed-mode reversed-phase and cation-exchange HPLC-MS/MS method and its application to pharmacokinetic studies.
abstract: A simple, fast and sensitive mixed-mode reversed-phase and cation-exchange HPLC-MS/MS method for the quantification of S-propargyl-cysteine (SPRC), a novel cardioprotective agent, has been developed and validated for preclinical studies. Chromatographic separation of SPRC and its internal standard (IS) was performed using a commercial analytical column which contained both C18 bonded silica particles and sulfonic acid cation-exchange particles. The optimized mobile phase was composed of acetonitrile/ammonium acetate buffer (10mM, pH 4): 30/70 (v/v). Quantification was conducted by multiple reaction monitoring (MRM) of the transitions of m/z 160.0 → 143.0 for SPRC and 178.1 → 160.9 for S-butyl-cysteine (IS). The assay utilized methanol to achieve a simple and fast deproteinization. The lower limit of quantification (LLOQ) was 0.6 μg/mL (diluted with 50-fold of methanol) using 20 μL rat plasma. The assay was linear over a range from 0.6 to 159 μg/mL, with intra- and inter-batch accuracy (as relative error) less than ± 5% and precision (as relative standard deviation) less than 10%. Using the validated assay, the pharmacokinetic properties of SPRC in rats were investigated. SPRC exhibits linear pharmacokinetics after oral or intravenous administration in rats. The bioavailability after oral administration at 25, 75, and 225 mg/kg was 96.6%, 97.0%, and 94.7%, respectively.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hongrui
authors.initials: H
authors.lastname: Liu
authors.forename: Guo
authors.initials: G
authors.lastname: Ma
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Tengfei
authors.initials: T
authors.lastname: Shao
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Yizhun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Weimin
authors.initials: W
authors.lastname: Cai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D005260:Female; D007275:Injections, Intravenous; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*
chemical_list: D002316:Cardiotonic Agents; C556437:S-propargylcysteine; D003545:Cysteine