title: Simple and sensitive LC-MS/MS-based assay for the quantification of dimemorfan in human plasma for use in a pharmacokinetic study.
abstract: 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.
authors.affiliation: Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Tan
authors.forename: Jinfu
authors.initials: J
authors.lastname: Peng
authors.forename: Qi
authors.initials: Q
authors.lastname: Pei
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Chengxian
authors.initials: C
authors.lastname: Guo
authors.forename: Ye
authors.initials: Y
authors.lastname: Hua
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Guoping
authors.initials: G
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000996:Antitussive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003371:Cough / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D009019:Morphinans / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D000996:Antitussive Agents; D009019:Morphinans; C012621:dimemorfan
keywords: LC-MS/MS; dimemorfan; human plasma; method validation; pharmacokinetics