title: A novel UPLC-ESI-MS/MS method for the quantitation of disulfiram, its role in stabilized plasma and its application.
abstract: Disulfiram (DSF) has been used to treat alcoholism for many years and it has been suggested to play a key role in combatting many kinds of tumors. However, disulfiram has complex pharmacokinetics and is rapidly eliminated which limits its use as a tumor treatment. Therefore, a rapid and sensitive analytical method based on ultra performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated for the determination of disulfiram in rat plasma. Blood samples were pre-stabilized with a stabilizing agent and then plasma was obtained and subjected to solid phase extraction (SPE), and chromatographed on a Phenomenex Kinetex(®) XB C18 column with gradient elution using a mobile phase consisting of acetonitrile-water (containing 0.1% formic acid and 1mM ammonium acetate) at a flow rate of 0.2mL/min for 3min. Multiple reactions monitoring in positive mode was carried out with disulfiram at 296.95/115.94 and diphenhydramine (internal standard, IS) at 256.14/167.02 over a linear range from 0.6 to 1200ng/mL. The extraction recovery of disulfiram for different concentrations ranged from 75.7% to 78.3%. The intra- and inter-day precision was less than 8.93% and 12.39%, respectively, and the accuracy was within ±7.75%. The validated method was successfully applied to a pharmacokinetic study of disulfiram in rat plasma after oral administration of a dose of 180mg/kg.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Jing
authors.forename: Yilin
authors.initials: Y
authors.lastname: Tang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004221:Disulfiram / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D004221:Disulfiram
keywords: Disulfiram; Electrospray ionization; Mass spectrometry; Pharmacokinetics; Ultra performance liquid chromatography