Simultaneous determination of AM80 (tamibarotene) and WJD-A-1 in rat plasma by ultra high-performance liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study. (31st October 2018)

• Record Type: Journal Article
• Authors: Leng, Ping; Yang, Zhao; Ma, Baohua; Li, Jing; Sun, Jialin; Xie, Yiming; Sun, Yong
• Is Part Of: Artificial cells, nanomedicine, and biotechnology. Volume 46(2018)Supplement 1
• Page Start: 1131
• Page End: 1137
• Publication Date: 2018-10-31
• Subjects: AM80 (tamibarotene) -- WJD-A-1 -- UHPLC–MS/MS -- rat plasma -- pharmacokinetics; Artificial cells -- Periodicals; Nanotechnology -- Periodicals; Blood substitutes -- Periodicals; Tissue engineering -- Periodicals; Molecules -- Periodicals; Biotechnology -- Periodicals; 615.39
• DOI: 10.1080/21691401.2018.1446443
• Languages: English
• ISSNs: 2169-1401

Abstract

Abstract: A compound (WJD-A-1) was previously reported as a candidate prodrug of Am80 (tamibarotene), which was approved in Japan in 2005 as a therapeutic agent for recurrent refractory acute promyelocytic leukaemia. A rapid, selective and sensitive ultra high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was developed for the first time to simultaneously determine WJD-A-1 and its major phase-I metabolites AM80 in rat plasma. After a simple sample preparation procedure by protein precipitation with methanol and acetonitrile, WJD-A-1, AM80 and the internal standard were chromatographed on an ACQUITY UPLC TM BEH C18 column. The mobile phase consisted of methanol–0.1% formic acid (80:20, v/v) and the flow rate was 0.20 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. Each plasma sample was chromatographed within 2.6 min. The linear calibration curves for WJD-A-1 and the AM80 were obtained in the concentration range of 5.40–5.40 × 10 3 and 5.08–5.08 × 10 3 ng/mL, respectively ( r ≥ 0.99). The intra- and inter-day precision (relative standard deviation, RSD) values were less than 8% and the accuracy (relative error, RE) was within ±6.8%, determined from quality control (QC) samples for the analytes. The method herein described was fully validated and successfully applied to pharmacokinetic study of WJD-A-1 following an intravenous administration of 300 μg/kg WJD-A-1 to rats.