LC-MS测定人血浆中盐酸舍曲林的浓度及相对生物利用度

 目的建立人血浆中盐酸舍曲林浓度的LC-ESI-MS测定方法,研究盐酸舍曲林在健康人体内的药动学行为,评价两种制剂的生物等效性。方法血浆样品经碱化后,环己烷提取,HPLC-ESI-MS内标法分析。检测离子为m/z 306.2(盐酸舍曲林加氢离子)、m/z 306.1(内标扎来普隆加氢离子)。20名健康受试者交叉口服供试片和参比片,剂量均为50 mg。结果盐酸舍曲林测定的线性范围为0.5～30μg·L^-1;盐酸舍曲林受试制剂和参比制剂的t_max分别为(4.8±0.8)和(5.1±1.3)h,ρ_max分别为(15.86±2.78)和(15.24±2.52)μg·L^-1,t_1/2分别为(29.53±5.40)和(29.32±5.02)h,AUC_{0～96 h}分别为(338.0±29.34)和(347.96±41.0)μg·h·L^-1。结论本法灵敏、准确、简便。统计学结果表明,两种制剂生物等效。

Determination of Sertraline in Human Plasma by LC-MS: Application to Relative Bioavailability of Domestic and Imported Sertraline Tablets

OBJECTIVE To develop a HPLC-ESI-MS assay for the determination of sertraline in human plasma and to investigate the pharmacokinetics and bioequivalence of two sertraline tablets in human.METHODS After being treated with 1 mol·L^-1 sodium hydroxide,plasma was processed by cyclohexane and compounds were separated on a reversed-phase C₁₈ column with a mobile phase of methanol-10(mmol·L^-1) ammonium acetate buffer solution (pH 3.5)-acetonitrile(62∶28∶10).HPLC-ESI-MS was performed with the selected-ion monitoring mode.Target ions were at m/z 306.2 for sertraline and at m/z 306.1 for the internal standard.A randomized cross-over design was performed in 20 healthy volunteers.In the two study periods,a single dose of 50 mg sertraline tablet was administered to each volunteer.RESULTS The calibration curve was linear over the range of 0.5～30 μg·L^-1.The main pharmacokinetic parameters of t_{maxρmax,t1/2 and AUC0～96 h were(5.1±1.3) h,(15.24±2.52) μg·L^-1,(29.32±5.02) h and(347.96±41.0) μg·h·L^-1 for the reference tablet;(4.8±0.8) h,(15.86±2.78) μg·L^-1,(29.53±5.40) h and(338.0±29.34) μg·h·L^-1 for the test tablet.The results of variance analysis and two one-side t-test showed that there was no significant difference between the two formulations in the AUC and ρmax.CONCLUSION The assay is proved to be sensitive,accurate and convenient.The two formulations are bioequivalent.}