Therapeutic drug monitoring is an important clinical testing of the drugs to monitor their concentrations in plasma in order to guarantee their optimal impact, and to avoid any side effects resulting from drug-drug interactions. A green reversed-phase high-performance liquid chromatographic method using a photodiode array detector (RP-HPLC-PDA) was developed for the simultaneous determination of three carbapenem antibiotics (Imipenem, ertapenem, and meropenem) with the co-formulated drug (cilastatin) and contraindicated drugs (probenecid and warfarin) in spiked human plasma. The separation was achieved at 25 °C using a gradient elution of a mixture of mobile phase A: methanol and mobile phase B: phosphate buffer (pH 3.0). The photodiode array detector was adjusted at 220 nm. Bioanalytical method validation was carried out as per the FDA guidelines, and the method showed good linearity ranges for the six drugs that included their Cmax levels along with low limits of quantification. Based on the results, the method was found to be accurate and precise; with high % recovery and good % RSD, respectively. The method was successfully applied to spiked human plasma, signifying a good potential to be implemented in future TDM studies of these drugs when co-administered together.

中文翻译：

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利用简单、绿色的RP-HPLC-PDA对六种禁忌/合用药物进行治疗药物监测；在加标人血浆中的应用

治疗药物监测是药物的一项重要临床测试，旨在监测药物在血浆中的浓度，以保证其最佳效果，并避免药物间相互作用产生的任何副作用。开发了一种使用光电二极管阵列检测器的绿色反相高效液相色谱方法（RP-HPLC-PDA），用于同时测定三种碳青霉烯类抗生素（亚胺培南、厄他培南和美罗培南）及其复方药物（西司他丁）以及在人血浆中添加禁忌药物（丙磺舒和华法林）。使用流动相 A：甲醇和流动相 B：磷酸盐缓冲液（pH 3.0）混合物的梯度洗脱在 25 °C 下实现分离。光电二极管阵列检测器调整为220 nm。生物分析方法验证是根据 FDA 指南进行的，该方法显示六种药物具有良好的线性范围，包括其 Cmax 水平和低定量限。结果表明，该方法准确、精密；分别具有高回收率和良好的 RSD %。该方法已成功应用于加标的人血浆，这表明在未来这些药物共同给药时的 TDM 研究中具有良好的应用潜力。