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目的:建立高效液相色谱-串联质谱联用法(LC-MS/MS)同时测定人尿中氨苄西林和氯唑西林浓度,研究健康人口服复方氨氯西林胶囊后的尿药排泄。方法:12名健康男性志愿者按3×3拉丁方顺序进行单剂口服给药后按设计时间点收集尿样。尿样加入曲马多为内标,甲醇沉淀蛋白后进样,分析氨苄西林和氯唑西林的浓度,色谱条件为:色谱柱:Shim-pack VP-ODS柱(150 mm×4.6 mm,5μm);流动相:甲醇-10 mmol·L~(-1)乙酸铵(68:32);流速:0.8 ml·min~(-1);采用等度洗脱进行分离,质谱检测采用多重反应监测(MRM)扫描。结果:氨苄西林和氯唑西林线性范围分别为:0.10～15.00μg·ml~(-1)和0.05～10.00μg·ml~(-1),线性关系均良好。准确度与精密度结果显示高、中、低三种浓度的氨苄西林和氯唑西林日间、日内变异均小于15%。24h内氨苄西林低、中、高剂量组的原形药物平均累积排泄率分别为(38.0±16.6)%,(31.7±15.9)%,(28.2±8.0)%;氯唑西林低、中、高剂量组平均累积排泄率分别为(11.3±3.9)%,(10.7±3.6)%,(11.2±4.3)%。结论:本法可用于同时测定人尿中氨苄西林和氯唑西林浓度,复方氨氯西林胶囊中氨苄西林在人体内排泄与单药时一致,氯唑西林在人体内主要以非原形药排泄。
OBJECTIVE: To establish a method for the simultaneous determination of ampicillin and cloxacillin in human urine by high performance liquid chromatography-tandem mass spectrometry (LC-MS / MS), and to study urinary excretion after oral administration of ampicillin capsules in healthy subjects. METHODS: Twelve healthy male volunteers were given a single oral dose of 3 × 3 Latin order to collect urine samples at design time points. Urinary samples were loaded with tramadol as an internal standard and samples were precipitated with methanol. The concentrations of ampicillin and cloxacillin were analyzed by column chromatography on a Shim-pack VP-ODS column (150 mm × 4.6 mm, 5 μm) The mobile phase was methanol-10 mmol·L -1 ammonium acetate (68:32), the flow rate was 0.8 ml · min -1. The isocratic elution was used for the separation. MRM) scan. Results: The linear ranges of ampicillin and cloxacillin were 0.10 ~ 15.00μg · ml -1 and 0.05 ~ 10.00μg · ml -1, respectively. The linear relationships were good. Accuracy and precision The results showed that the intra-day and intra-day variations of ampicillin and cloxacillin in high, medium and low concentrations were all less than 15%. The average cumulative excretion rates of prototype drugs in low, middle and high dose ampicillin groups were (38.0 ± 16.6)%, (31.7 ± 15.9)% and (28.2 ± 8.0)%, respectively. The low, medium and high doses of cloxacillin The average cumulative excretion rate was (11.3 ± 3.9)%, (10.7 ± 3.6)% and (11.2 ± 4.3)%, respectively. Conclusion: This method can be used to simultaneously determine the concentrations of ampicillin and cloxacillin in human urine. Ampicillin in compound amoxicillin capsules is excreted in the human body in consistent with monotherapy, and cloxacillin is mainly excreted as non-prototype drug in the human body.