A validated HPLC–MS/MS method for the quantification of supinoxin in rat plasma and its application to pharmacokinetic study

Acta Chromatographicae

Kang Nam Sook¹  Kim Hye-Rim¹  Hyun Hun-Chan¹  Koo Tae-Sung²  Jeong Jong-Woo³  Seol Yun-Hwan³  Lee Jong-Hwa⁴  Gong Young-Dae⁵ 

[1] 1Graduate School of New Drug Discovery and Development, Chungnam National University, Republic of Korea;1Graduate School of New Drug Discovery and Development, Chungnam National University, Republic of KoreaAuthor for correspondence: [e-mail];1Graduate School of New Drug Discovery and Development, Chungnam National University, Republic of Korea†These authors contributed equally to this work.;2Applied Toxicology Research Center, Korea Institute of Toxicology, Republic of Korea;3Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University Republic of Korea

关键词: Supinoxin;    RX-5902;    LC–MS/MS;    P-p68;    pharmacokinetics;   

DOI  :  10.1556/1326.2016.00056

学科分类：化学（综合）

来源: Akademiai Kiado Rt.

【 摘 要 】

A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the quantification of an anticancer drug, supinoxin (RX-5902), in rat plasma. Following precipitation pretreatment using 0.1% formic acid in acetonitrile, separation was performed using a reverse phase liquid chromatography column packed with C18 (3.5 μm, 2.1 × 50 mm) along with a mobile phase of 0.1% formic acid in distilled water and 0.1% formic acid in acetonitrile at a flow rate of 0.3 mL min−1. Detection was achieved using MS/MS by multiple reaction monitoring via an electrospray ionization source at mass/charge transitions of m/z 442.30 → 223.30 for supinoxin and m/z 430.08 → 223.20 for the internal standard DGG-200064. This method demonstrated a linear standard curve (r = 0.9980) over a supinoxin concentration range of 0.0005–1 μg mL−1, as well as intra- and inter-assay precisions below 7.08% and 13.74%, respectively, and an accuracy of 1.15–4.50%. The matrix effect, recovery, and process efficiency were 93.63%, 99.70%, and 93.33%, respectively. Thus, a sensitive and reliable LC–MS/MS method was developed and validated for the quantification of supinoxin in rat plasma. This method was successfully applied to the evaluation of pharmacokinetic studies after single intravenous and oral administration of 1 mg kg−1 supinoxin in rats.

【 授权许可】

Unknown