HPLC-FLD法测定血浆中阿仑膦酸钠的浓度及药代动力学研究

目的建立血浆中阿仑膦酸钠的HPLC-FLD检测方法,并应用于药动学研究。方法采用Kromasil-C18柱（4.6 mm×150 mm,5μm）;流动相：甲醇-乙腈-柠檬酸-焦磷酸钠体系;流速：1.5 ml·min^-1;柱温：35℃;激发波长：（λex）=260 nm,发射波长：（λem）=310 nm。24名健康男性志愿者单剂量口服阿仑膦酸钠片,测定血浆药物浓度,计算药代动力学参数。结果阿仑膦酸钠在1~100 ng·ml^-1范围内线性关系良好（r=0.9999）,最低定量限为1 ng·ml^-1。阿仑膦酸钠的专属性强,日内、日间精密度和准确度良好。结论本文研究建立了阿仑膦酸钠在血浆中HPLC-FLD的检测方法,该方法灵敏、准确,可用于临床药动学及生物等效性研究。

Determination of Alendronate Sodium in Plasma by HPLC via Fluorescence Detector and Pharmacokinetic Study

Objective To establish a reliable analytical method for pharmacokinetic studies of alendronate sodium in human plasma by an HPLC system with a fluorescence detector. Methods Liquid chromatography was performed on a Kromasil CIS column （4.6 mm×150mm,5 μm）. The mobile phase was as a mixed system that consisted of methanol/acetonitrile/citric/acid/pyrophosphate sodium with gradient elution at a flow-rate of 1.5 ml.min^-1. The column temperature was set at 35 ℃. The excitation and emission wavelengths were set at 260 nm and 310 nm. A single oral dose of alendronate sodium was given to 24 healthy male volunteers. The plasma concentration of the drug was determined, and pharmacokinetic parameters were analyzed. Results The method validation was ac- complished through recovery, linearity, quantification limit, precision, accuracy, specificity, and stability. The linear range was 1 - 100 ng -ml^-1 （ r = 0. 9999）. The quantification limit was 1 ng .ml^-1. Conclusion This study has established an HPLC-FLD detection method for alendronate in plasma. This method is sensitive and accurate, which can be used for clinical pharmacokinetic and bioequivalence studies.