A simple, sensitive and cost‐effective HPLC‐UV bioanalytical method for determination of lopinavir (LPV) in rat and human plasma was developed and validated. The plasma sample preparation procedure includes a combination of protein precipitation using cold acetonitrile and liquid–liquid extraction with n‐hexane–ethyl acetate (7:3, v/v). A good chromatographic separation was achieved with a Phenomenex Gemini column (C₁₈, 150 mm × 2.0 mm, 5 μm) at 40°C with gradient elution, at 211 nm. Calibration curves were linear in the range 10–10,000 ng/mL, with a lower limit of quantification of 10 ng/mL using 100 μL of plasma. The accuracy and precision in all validation experiments were within the criteria range set by the guidelines of the Food and Drug Administration. This method was successfully applied to a preliminary pharmacokinetic study in rats following an intravenous bolus administration of LPV. Moreover, the method was subsequently fully validated for human plasma, allowing its use in therapeutic drug monitoring (TDM). In conclusion, this novel, simple and cost‐efficient bioanalytical method for determination of LPV is useful for pharmacokinetic and drug delivery studies in rats, as well as TDM in human patients.

中文翻译：

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开发和验证一种经济高效且灵敏的生物分析HPLC-UV方法，用于测定大鼠和人血浆中的洛匹那韦。

开发并验证了一种简单，灵敏且经济高效的HPLC-UV生物分析方法测定大鼠和人血浆中的洛匹那韦（LPV）。血浆样品制备过程包括使用冷的乙腈和液-液萃取用蛋白质沉淀的组合Ñ己烷-乙酸乙酯（7:3，V / V）。使用Phenomenex Gemini色谱柱（C ₁₈（150 mm×2.0 mm，5μm），在40°C于211 nm梯度洗脱。校正曲线在10–10,000 ng / mL范围内呈线性，使用100μL血浆的定量下限为10 ng / mL。所有验证实验的准确性和精密度均在美国食品药品管理局（FDA）规定的标准范围内。在静脉推注LPV后，该方法已成功应用于大鼠的初步药代动力学研究。此外，该方法随后针对人体血浆进行了充分验证，从而可用于治疗药物监测（TDM）。总之，这种新颖，简单且经济高效的LPV测定方法可用于大鼠的药代动力学和药物递送研究以及人类患者的TDM。