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目的建立人血浆中普卢利沙星活性代谢产物NM394检测的HPLC法,并进行其在人体内药动学的研究。方法10名健康受试者单剂量口服200 mg普卢利沙星片后,采集一系列血样,检测其血药浓度。血浆经高氯酸沉淀蛋白,以ZORBAXEclipse XDB-C_(18)(150 mm×4.6 mm,5μm)为色谱柱,流动相为乙腈-2%醋酸-水=20:40:40(V/V/V),流速为0.8 mL·min~(-1),柱温为25℃,检测波长为278 nm。结果NM394在血药浓度0.05～7.50 mg·L~(-1)内线性关系良好(r=0.999 9),定量下限为0.05 mg·L~(-1);低、中、高3个浓度的相对回收率(n=5)分别为(105.16±1.86)%、(105.01±1.94)%、(100.40±4.53)%,日内RSD(n=5)分别为5.57%、2.36%、2.31%,日间RSD(n=5)分别为3.25%、2.22%、4.26%。药动学参数分别为:ρ_(max)(1.480±0.329)mg·L~(-1),t_(max)(0.825±0.374)h,AUC_(0→t)(6.853±1.679)mg·h·L~(-1),AUC_(0→∞)(7.488±1.687)mg·h·L~(-1)。结论本方法简便、灵敏、快速、准确,适用于人血浆中普卢利沙星活性代谢产物NM394浓度的检测及其药动学研究。
Objective To establish a HPLC method for the determination of promethacin active metabolite NM394 in human plasma and study its pharmacokinetics in human. Methods A total of 10 healthy volunteers received a single oral dose of prulifloxacin 200 mg. A series of blood samples were collected and plasma concentrations were measured. The plasma was precipitated with perchloric acid and the chromatographic column was ZORBAXEclipse XDB-C 18 (150 mm × 4.6 mm, 5 μm). The mobile phase was acetonitrile-2% acetic acid-water = 20:40:40 (V / V / V) at a flow rate of 0.8 mL · min ~ (-1). The column temperature was 25 ℃ and the detection wavelength was 278 nm. Results The linear range of NM394 was 0.05 ~ 7.50 mg · L -1 (r = 0.999 9) and the lower limit of quantitation was 0.05 mg · L -1. The concentrations of NM394 in low, middle and high concentrations The relative recoveries were (105.16 ± 1.86)%, (105.01 ± 1.94)%, (100.40 ± 4.53)% and intraday RSD (n = 5) were 5.57%, 2.36%, 2.31% The inter-RSD (n = 5) was 3.25%, 2.22% and 4.26% respectively. The pharmacokinetic parameters were as follows: ρ max (1.480 ± 0.329) mg · L -1, t max 0.825 ± 0.374 h, AUC 0 -6 t 6.853 ± 1.679 mg · h · L -1, AUC 0 -0 ∞ (7.488 ± 1.687) mg · h · L -1. Conclusion The method is simple, sensitive, rapid and accurate and is suitable for the determination of promethacin active metabolite NM394 in human plasma and its pharmacokinetics.