目的 采用液相色谱-串联质谱法测定人血浆中二甲双胍的浓度。 方法 血浆样品用乙腈（含0.1%甲酸）沉淀蛋白后用二氯甲烷反洗后进行分析。使用Agilent C8（75 mm×4.6 mm，3.5 μm）色谱柱。流动相：A泵：5 mmol/L醋酸铵（三乙胺调pH值至7.5），B泵：乙腈。线性梯度洗脱，流速0.4 mL/min。采用电喷雾离子源，多反应离子监测。用于定量分析的离子对二甲双胍为130.2/71.1，内标吗啉胍为172.2/60.2。 结果 线性范围为50～2 000 ng/mL，最低定量限为50 ng/mL，预处理回收率为81.7%～98.0%，二甲双胍的基质效应＜9.97%，日内和日间相对标准偏差均＜5.2%。 结论 液相色谱-串联质谱法快速、简便、灵敏度高，是一种适用于人血浆中药物浓度的测定及药物动力学和生物利用度研究的方法。
ObjectiveTo study the pharmacokinetics of lovastatin/niacin sustained-release tablets in healthy Chinese volunteers. MethodsEligible subjects were enrolled to receive a single dose of 20/500, 20/750 and 20/1 000 mg lovastatin/niacin sustained-release tablets and multiple dose of 20/1 000 mg lovastatin/niacin sustainedrelease tablets, one time per day, sustained for 5 days, respectively. Blood samples were obtained before dosing and up to 10, 20, 30, and 45 minutes, and 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, and 15 hours after dosing. Niacin, niacinamide, nicotinuric acid and lovastatin were detected by high performance liquid chromatography-tandem mass spectrometry method. ResultsThe peak concertration and the area under the plasma concentration-time curve (0-t) of nicotinuric acid had linear dynamics characteristics with the dosage when the dose of niacin was between 500 and 1 000 mg. After multiple dosing, pharmacokinetics parameters of nicotinuric acid and lovastatin were close. No significant diTherence was found between male and female subjects. ConclusionLovastatin/niacin sustained-release tablets possess linear kinetics. Accumulation is not significant after multiple dosing. Gender doesn't affect the pharmacokinetics parameters.
ObjectiveTo establish an accurate and sensitive high performance liquid chromatography-mass spectrometric (HPLC/MS/MS) method for determination of vorinostat (SHA) and M2 metabolites in human serum, which was applicable for pharmacokinetic study of SHA. MethodsThe essay was conducted with an API 3000 HPLC-MS/MS system consisted of a Gemini C18 column (50 mm×3 mm, 3 μm), and the mobile phase consisted of methanol-acetonitrile-water-1 mol/L NH3-formic acid (25:15:60:0.1:0.05) at a flow rate of 0.23 mL/min. Acidulated serum samples were extracted by 3.5 mL diethyl ether which contains 3% isopropyl alcohol and was operated under the multiple reaction monitoring mode using the electrospray ionization technique. d5-SHA was used as the internal standard. ResultsThe retention time of SHA, M2 metabolite and internal standard were 4.1, 3.1 and 4.0 minutes, respectively. The linear range of SHA and M2 metabolite were in the range of 1-1 000 and 2-2 000 ng/mL, and the limit of quantity were 1.0 and 2.0 ng/mL; the method recovery were 93.0%-99.3% and 88.11%-104.12%, respectively. Matrixes effect of SHA and M2 metabolite were blow 9.0%. ConclusionThis method for the quantitative determination of SHA and M2 in human serum was proved to be simple, rapid, sensitive and accurate; it can be applied in the determination of SHA and M2 metabolite.