健康志愿者单次口服昂丹司琼口腔溶解薄膜人体药动学和生物等效性研究  

Study of Pharmacokinetics and Bioequivalence of Single Oral Dose Ondansetron Dissolved Film in Healthy Volunteers

作　　者：蒋俊毅[1] 林慧[1] 曹蓓[1] 钱薇[1] 肖大伟[1] 

机构地区：[1]南京大学医学院附属鼓楼医院药物Ⅰ期临床实验室,江苏南京210008

出　　处：《中国药物警戒》2016年第11期663-669,共7页Chinese Journal of Pharmacovigilance

摘　　要：目的建立并验证灵敏、可靠的高效液相色谱-串联质谱(LC-MS-MS)法测定昂丹司琼人体血药浓度,评价昂丹司琼口腔溶解薄膜的生物等效性。方法血浆中精密加入内标溶液,混匀后加入0.5 m L甲基叔丁基醚进行液-液萃取,混旋并离心后取上清液,氮气吹干后用100μL流动相复溶,离心后取10μL上清进样进行LC-MS/MS分析。采用ZORBAX SB-C18 2.1 mm×50 mm 3.5μm色谱柱,以0.1%甲酸水溶液及甲醇为流动相,采用电喷雾离子源,在多离子检测模式下进行质谱分析。结果昂丹司琼在人体血浆中最低定量限为0.2 ng·m L-1。日内及日间精密度考察结果,其变异度分别低于5.94%及6.22%。结论本方法专属、灵敏、准确,可成功应用于健康中国人体内昂丹司琼药动学及生物等效性研究。Objective To develop and validate a sensitive and reliable liquid chromatography-tandem mass/mass spectrometry（LC-MS/MS） method for the determination of ondansetron in human plasma and evaluate the bioequivalence of oral ondansetrondissolved film. Methods The method involved the addition of internal standard solution to plasma samples, followed by liquidliquidextraction with 0.5 mL of ethyl acetate. After vortexing and centrifugation, supernatant was transferred and evaporatedto dryness in a slight stream of nitrogen. The residue was dissolved in 100 μL of mobile phase, and 10 μl of it was used for LCMS/MS analysis. The separations were performed on a ZORBAX SB-C18 2.1 mm×50 mm 3.5 μm, with 0.1% formic acid andmethyl alcohol as mobile phase, and the detection was performed on tandem mass/mass spectrometry by the multiple-reactionmonitoring via an electrospray ionization source. Results The standard curve was linear over the concentration range from 0.2to 80 ng·mL-1. The lower limit of quantification was 0.2 ng·mL-1 using 100 μL of human plasma sample. The intra- and interassayprecision and accuracy were found to be less than 5.94% and 6.22%, respectively. Conclusion This developed analyticalmethod was successfully applied to the pharmacokinetics and bioequivalence study of ondansetron in healthy Chinese volunteers.

关 键 词：昂丹司琼 生物等效性 药动学 高效液相色谱-串联质谱(LC-MS-MS) 生物利用度 

分 类 号：R927[医药卫生—药学]