Simple and sensitive LC-MS/MS-based assay for the quantification of dimemorfan in human plasma for use in a pharmacokinetic study

• Published in: Biomedical chromatography Vol. 29; no. 5; pp. 647 - 653
• Main Authors: Tan, Hongyi, Peng, Jinfu, Pei, Qi, Yang, Liu, Chen, Jun, Guo, Chengxian, Hua, Ye, Yuan, Hong, Yang, Guoping
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2015
• Subjects: Adolescent; Adult; Antitussive Agents - blood; Antitussive Agents - pharmacokinetics; Antitussive Agents - therapeutic use; Chromatography, High Pressure Liquid - methods; Cough - drug therapy; dimemorfan; Female; human plasma; Humans; LC-MS/MS; Male; method validation; Morphinans - blood; Morphinans - pharmacokinetics; Morphinans - therapeutic use; pharmacokinetics; Sensitivity and Specificity; Tandem Mass Spectrometry - methods; Young Adult; method validation; dimemorfan; pharmacokinetics; LC-MS/MS; human plasma
• ISSN: 0269-3879; 1099-0801; 1099-0801
• DOI: 10.1002/bmc.3325

Dimemorfan phosphate has been widely used for 40 years throughout the world for the treatment of coughs. This is the first report on the use of an LC‐MS/MS‐based assay for the determination of dimemorfan in human plasma using estazolam as an internal standard after one‐step protein precipitation with acetonitrile. Chromatographic separation was achieved on a Phenomenex Luna C18 column (3 µm, 50 × 2.0 mm) using a fast gradient method, which involves water and methanol as the mobile phase (both containing 0.1% formic acid). Dimemorfan and estazolam were detected with proton adducts at m/z values of 255.8 → 155.1 and 295.0 → 267.0, respectively, in the selected reaction monitoring positive mode. The linear dynamic range of the assay was 0.04–5.00 ng/mL. The chromatographic run time for each plasma sample was <5 min. The method was proven to be accurate, precise, and repeatable. Finally, the developed method was successfully applied for the determination of dimemorfan in a pharmacokinetic study using healthy Chinese subjects. Copyright © 2014 John Wiley & Sons, Ltd.