Granich G G, Eveland M R, Krogstad D J
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Antimicrob Agents Chemother. 1989 Aug;33(8):1275-9. doi: 10.1128/AAC.33.8.1275.
We report a fluorescence polarization immunoassay (FPIA) for zidovudine (azidothymidine; Retrovir). This assay is accurate and specific over the clinically relevant range of zidovudine concentrations in serum (from 1 to 1,250 ng/ml; from 0.004 to 4.8 microM) and is unaffected by potentially interfering compounds in the sera of patients with renal or hepatic failure. Cross-reactivity with structural analogs of zidovudine (including zidovudine glucuronide) is less than 0.05%, except for cross-reactivities of 0.2, 0.3, and 0.4% with 3-methylthymidine, 3',5'-dideoxythymidine, and A22U (the optical isomer of zidovudine), respectively. The FPIA for zidovudine is more sensitive and more specific than high-performance liquid chromatography (HPLC); it requires 50 to 60 or 200 versus 500 microliters of serum and is faster to perform (45 specimens per h with the FPIA versus 3 specimens per h with HPLC). The zidovudine FPIA compares well with the radioimmunoassay. A correlation coefficient of 0.992 was observed with 31 serum specimens examined by both methods. All three assays (FPIA, radioimmunoassay, and HPLC) are unaffected by the heat treatment used to inactivate human immunodeficiency virus. The zidovudine FPIA should be particularly useful for analyzing specimens from large numbers of human immunodeficiency virus-infected patients receiving zidovudine in current clinical trials.
我们报道了一种用于齐多夫定（叠氮胸苷；Retrovir）的荧光偏振免疫测定法（FPIA）。该测定法在血清中齐多夫定浓度的临床相关范围内（1至1250 ng/ml；0.004至4.8 microM）准确且特异，并且不受肾衰竭或肝功能衰竭患者血清中潜在干扰化合物的影响。与齐多夫定结构类似物（包括齐多夫定葡糖醛酸）的交叉反应率小于0.05%，但与3 - 甲基胸苷、3',5'-二脱氧胸苷和A22U（齐多夫定的旋光异构体）的交叉反应率分别为0.2%、0.3%和0.4%。齐多夫定的FPIA比高效液相色谱法（HPLC）更灵敏、更特异；它需要50至60微升或200微升血清，而HPLC需要500微升血清，且FPIA执行速度更快（FPIA每小时检测45个样本，而HPLC每小时检测3个样本）。齐多夫定FPIA与放射免疫测定法相比效果良好。用两种方法检测31份血清样本时，观察到相关系数为0.992。所有三种测定法（FPIA、放射免疫测定法和HPLC）均不受用于灭活人类免疫缺陷病毒的热处理的影响。在当前的临床试验中，齐多夫定FPIA对于分析大量接受齐多夫定治疗的人类免疫缺陷病毒感染患者的样本应该特别有用。
