HPLC_FLD法测定血浆中阿仑膦酸钠的浓度及药代动力学研究.docx

HPLC-FLD 法测定血浆中阿仑膦酸钠的浓度及药代动力学研究单婷婷① ，孙 燕② ，吴 媛③ ，董瑞华③ ，刘泽源③［摘 要］ 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，5 μm) ; 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: (λ ex)=260 nm，发射波长: ( λ em) = 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。［关键词］ 阿仑膦酸钠; HPLC-FLD; 药代动力学［中图分类号］ Ｒ927． 2; Ｒ969． 1［文献标志码］ A［文章编号］ 1008-9926( 2014) 5-0402-4［DOI］ 10． 3969 / j． issn． 1008-9926． 2014． 05． 006Determination of Alendronate Sodium in Plasma by HPLC viaFluorescence Detector and Pharmacokinetic StudySHAN Ting-ting① ，SUN Yan② ，WU Yuan③ ，DONG Ｒui-hua③ ，LIU Ze-yuan③① Institute for Drug and Instrument Control of PLA，Beijing 100166，China;② Troops Hospital 69240 of PLA，Urumqi 830011，China; ③ Department of Clinical Pharmacology，Affiliated Hospital，Academy of Military Medical Sciences，Beijing 100071，China［Abstract］ Objective To establish a reliable analytical method for pharmacokinetic studies of alendronatesodium in human plasma by an HPLC system with a fluorescence detector． Methods Liquid chromatography was performed on a Kromasil C18 column ( 4． 6 mm × 150 mm，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 and310 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