Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Oct 15;937:54-9. doi: 10.1016/j.jchromb.2013.08.009. Epub 2013 Aug 20.
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.
双硫仑（DSF）多年来一直被用于治疗酗酒，并且有人提出它在对抗多种肿瘤方面发挥着关键作用。然而，双硫仑的药代动力学复杂，且迅速被消除，这限制了其作为肿瘤治疗的用途。因此，开发并验证了一种基于超高效液相色谱-电喷雾串联质谱（UPLC-ESI-MS/MS）的快速灵敏的分析方法，用于测定大鼠血浆中的双硫仑。将含有稳定剂的血样预稳定，然后获得血浆并进行固相萃取（SPE），在 Phenomenex Kinetex(®) XB C18 柱上进行色谱分离，采用乙腈-水（含 0.1%甲酸和 1mM 乙酸铵）作为流动相进行梯度洗脱，流速为 0.2mL/min，洗脱时间为 3min。采用正离子多反应监测模式，双硫仑的监测离子对为 296.95/115.94，内标二苯海拉明的监测离子对为 256.14/167.02，线性范围为 0.6-1200ng/mL。不同浓度下双硫仑的提取回收率为 75.7%-78.3%。日内和日间精密度均小于 8.93%和 12.39%，准确度在±7.75%范围内。该验证方法成功应用于大鼠口服 180mg/kg 剂量后双硫仑的药代动力学研究。
