An efficient and reliable method using LC–MS/MS was established and validated for the simultaneous quantification of meropenem and imipenem in rat plasma. An electronic spray ion source in the positive multiple reaction monitoring mode was used for the detection and the transitions were m/z 384.6 → m/z 141.2 for meropenem, m/z 300.1 → m/z 141.8 for imipenem and m/z 423.4 → m/z 207.1 for matrine (IS). The calibration curves of meropenem and imipenem were linear in the range of 0.50–200 μg/mL. Satisfactory separation was achieved with a total run time of 3.0 min, the injection volume was 3 μl. The retention times of meropenem, imipenem and IS were 1.19, 1.14 and 1.13 min, respectively. Meropenem and imipenem are easily hydrolyzed in plasma. HEPES was used as a stabilizer and added to the plasma samples immediately after centrifugation. Extractions of meropenem, imipenem and IS were carried out by protein precipitation with acetonitrile. The specificity, precision and accuracy, stability, recovery and matrix effects were within acceptance limits. This method was successfully applied to investigate the pharmacokinetics of intravenous injection of meropenem and imipenem single administration or combined with sulbactam in rats. We found that sulbactam has no influence on the pharmacokinetics behavior of meropenem or imipenem.

中文翻译：

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LC-MS/MS同时测定大鼠血浆中美罗培南和亚胺培南及其在药代动力学研究中的应用

建立并验证了一种使用 LC-MS/MS 的有效且可靠的方法，用于同时定量大鼠血浆中的美罗培南和亚胺培南。采用正向多反应监测模式的电子喷雾离子源进行检测，离子对为美罗培南m/z 384.6 →  m/z 141.2，亚胺培南m/z 300.1 →  m/z 141.8 和m/z 423.4 →  m/z207.1 用于苦参碱 (IS)。美罗培南和亚胺培南的校准曲线在 0.50–200 μg/mL 范围内呈线性。总运行时间为 3.0 分钟，进样量为 3 μl，实现了令人满意的分离。美罗培南、亚胺培南和 IS 的保留时间分别为 1.19、1.14 和 1.13 分钟。美罗培南和亚胺培南在血浆中很容易水解。HEPES 用作稳定剂并在离心后立即添加到血浆样品中。美罗培南、亚胺培南和 IS 的提取是通过用乙腈进行蛋白质沉淀来进行的。特异性、精密度和准确度、稳定性、回收率和基质效应均在可接受范围内。该方法成功应用于大鼠静脉注射美罗培南和亚胺培南单次或联合舒巴坦的药代动力学研究。我们发现舒巴坦对美罗培南或亚胺培南的药代动力学行为没有影响。