Abstract This work is focused on the simultaneous determination of different nucleosides (lamivudine, abacavir, zidovudine) and non-nucleoside (nevirapine, efavirenz) reverse transcriptase inhibitors (antiretrovirals) in river, tap and well water by pH-gradient flow-injection analysis with diode-array detection (FIA-DAD) and further multivariate curve resolution-alternating least square (MCR-ALS) processing. Previous to the development of the analytical method with quantitative purpose, the acid-base characterization was conducted for all the analytes by determination of the experimental pKa. The pKa values, obtained by UV spectrometric titration coupled to MCR-ALS data modeling, were in agreement with those found in the literature, and, interestingly, a non-reported pKa of 12.27 was identified for nevirapine. Eventually, the analytical method was developed and its performance on the quantitation of the antiretrovirals was evaluated through its application to validation and environmental samples. The recovery studies showed values between 85 and 115% with relative errors of prediction below 10%. The figures of merit were satisfactory for all the studied drugs, with limits of detection between 25 and 40 μg L−1. Therefore, the proposed method, which is based on the generation of high-throughput data, is a simple and suitable alternative to determine the concentration of antiretroviral drugs in complex matrices, without pre-concentration or extraction steps. Additionally, MCR-ALS demonstrated to be a useful tool for solving mixtures of analytes with high spectral overlapping, in the presence of unknown interferences.

中文翻译：

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用于同时测定水中多种抗逆转录病毒药物的高通量化学计量辅助流动注射方法

摘要 本工作的重点是通过 pH 梯度流动注射分析法同时测定河流、自来水和井水中的不同核苷（拉米夫定、阿巴卡韦、齐多夫定）和非核苷（奈韦拉平、依法韦仑）逆转录酶抑制剂（抗逆转录病毒药物）。二极管阵列检测 (FIA-DAD) 和进一步的多元曲线分辨率交替最小二乘 (MCR-ALS) 处理。在开发具有定量目的的分析方法之前，通过测定实验 pKa 对所有分析物进行酸碱表征。通过结合 MCR-ALS 数据建模的紫外光谱滴定获得的 pKa 值与文献中发现的一致，有趣的是，奈韦拉平的未报告 pKa 值为 12.27。最终，开发了该分析方法，并通过将其应用于验证和环境样品来评估其在抗逆转录病毒药物定量方面的性能。回收率研究显示值介于 85% 和 115% 之间，预测的相对误差低于 10%。所有研究药物的品质因数都令人满意，检测限在 25 到 40 μg L-1 之间。因此，所提出的方法基于高通量数据的生成，是一种简单且合适的替代方法，可用于确定复杂基质中抗逆转录病毒药物的浓度，无需预浓缩或提取步骤。此外，在存在未知干扰的情况下，MCR-ALS 被证明是解决具有高光谱重叠的分析物混合物的有用工具。