Multiresponse optimization approach to develop a simple isocratic, highly sensitive and accurate HPLC method for the simultaneous determination of Efavirenz, Atazanavir, Lopinavir and Ritonavir in human blood plasma along with carvedilol as an internal standard. Optimized the factors (ACN, buffer concentration and flow rate) effecting and interacting with the responses (k1, Rs2,1, Rs3,2 and tR5) applying Central Composite Design a chemometric tool. All the mathematical models as well as response surfaces were defined and derived for the separation using this strategy. Chromatography was performed on Thermo Hypersil C18 column using mobile phase comprising of ACN: 10 mM KH2PO4 (51.2:48.8) with 1 mL min−1 flow rate and detection wavelength was fixed at 210 nm. The analysis time was within 9 min. The method developed was validated by following “Bioanalytical method validation” [USFDA-CDER, 2001]. The developed method can be applied for bioavailability and pharmacokinetic studies.

中文翻译：

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HPLC 方法的多响应优化：人血浆中蛋白酶抑制剂和 NNRTI 的同时估计

多响应优化方法开发一种简单的等度、高灵敏度和准确的 HPLC 方法，用于同时测定人血浆中的依法韦仑、阿扎那韦、洛匹那韦和利托那韦以及作为内标的卡维地洛。应用 Central Composite Design 化学计量工具优化了影响响应（k1、Rs2,1、Rs3,2 和 tR5）并与之相互作用的因素（ACN、缓冲液浓度和流速）。所有的数学模型以及响应面都被定义和推导出来使用这种策略进行分离。在 Thermo Hypersil C18 柱上进行色谱分析，使用的流动相由 ACN: 10 mM KH2PO4 (51.2:48.8) 组成，流速为 1 mL min-1，检测波长固定为 210 nm。分析时间在 9 分钟内。所开发的方法按照“生物分析方法验证”[USFDA-CDER, 2001] 进行了验证。所开发的方法可用于生物利用度和药代动力学研究。