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目的:建立HPLC-DAD法同时测定血浆中磺胺甲唑(SMZ)与甲氧苄啶(TMP)浓度,用于临床肺孢子菌肺炎(PCP)患者治疗药物监测。方法:200μL血浆样本经60μL10%高氯酸蛋白沉淀,离心后取上清液30μL进样。色谱柱为Kromasil 100-5-C_8(4.6×150 mm,5μm),流动相为甲醇–0.1 mol·L~(-1)乙酸铵(35:65),流速为0.9 m L·min~(-1),柱温为35℃,紫外检测波长为240 nm。采集20名经口服复方新诺明(0.48 g/次,3次/d)的PCP患者不同时间点共51份血浆样本,测定浓度。结果:在所建立的色谱条件下,磺胺甲唑、甲氧苄啶与各杂质分离良好,单次分析时间为6 min/样本。两待测物线性范围均为1~300μg·m L~(-1),最低检测限为1μg·m L~(-1)。通过10名PCP患者(取血点n≥3)浓度测定结果确定1 h时间点为峰浓度取血点,统计所有患者1 h时间点血药浓度结果,磺胺甲唑峰浓度均值为(131.9±41.3)μg·m L~(-1),甲氧苄啶峰浓度均值为(6.3±2.0)μg·m L~(-1)。参照目标范围浓度,仅55.0%的患者达标,其余需剂量调整。结论:此法操作简单,准确、精密度好,适用于临床PCP患者复方磺胺甲唑的治疗药物监测。
Objective: To establish a HPLC-DAD method for the simultaneous determination of plasma concentrations of sulfamethoxazole (SMZ) and trimethoprim (TMP) in patients with clinical Pneumocystis pneumonia (PCP). Methods: 200μL plasma samples were precipitated with 60μL of 10% perchloric acid protein and 30μL supernatant was injected after centrifugation. The chromatographic column was Kromasil 100-5-C_8 (4.6 × 150 mm, 5μm). The mobile phase was methanol-0.1 mol·L -1 ammonium acetate (35:65) at a flow rate of 0.9 m L · min ~ (- 1). The column temperature was 35 ℃ and UV detection wavelength was 240 nm. A total of 51 plasma samples from 20 PCP patients receiving oral cotrimoxazole (0.48 g / time, 3 times / d) were collected at different time points to determine the concentration. Results: Under the established chromatographic conditions, the separation of sulfamethoxazole and trimethoprim from each impurity was good. The single analysis time was 6 min per sample. The linear range of the two analytes was 1 ~ 300μg · m L -1, the lowest detection limit was 1μg · m L -1. 10 PCP patients (blood spot n≥3) concentration determination results to determine the time point of 1 h peak concentration of blood collection points, all patients at 1 h time point plasma concentration results, the average concentration of sulfamethoxazole (131.9 ± 41.3) μg · m L -1, and the mean concentration of trimethoprim was (6.3 ± 2.0) μg · m L -1. With reference to the target range of concentration, only 55.0% of patients meet the standard, the rest need to adjust the dose. Conclusion: This method is simple, accurate and precise, and is suitable for the monitoring of compound sulfamethoxazole in clinical PCP patients.