妥舒沙星人体血药浓度测定及药代动力学研究.docVIP

妥舒沙星人体血药浓度测定及药代动力学研究 　　【摘要】 目的 建立反相高效液相色谱荧光检测法测定人血浆中妥舒沙星浓度的方法。方法以加替沙星为内标，血浆经酸化采用20%高氯酸提取，色谱柱为XDB C18柱（4.6 mm×150 mm，5 μm）；流动相为乙腈甲醇20 mmol#8226;L-1磷酸二氢钾（15∶15∶70），荧光检测(λex=342 nm，λem=420 nm)。结果 妥舒沙星血浆浓度在10.80~1296 ng#8226;ml-1内具有良好线性关系，平均相对回收率大于95%，萃取回收率大于60%，日内、日间相对标准差（RSD）均小于4.3%。结论该方法灵敏、准确，可用于妥舒沙星的药动学研究。 　　【关键词】 高效液相色谱荧光法；妥舒沙星；血浆 　　文章编号：1003-1383(2010)06-0675-04 中图分类号：R 927.2 文献标识码：A 　　doi:10.3969/j.issn.1003-1383.2010.06.010 　　 　　Determination of tosufloxacin in human plasma by reversedphase highperformance 　　liquid chromatographic fluorometry 　　HUANGShiqian 　　（Medical School Affiliated Hospital of Guangxi Guidong, Wuzhou 543100） 　　【Abstract】 ObjectiveA sensitive liquid chromatographic fluorometry was developed for the determination of the active metabolite of tosufloxacin. 　　Methods Gatifloxacin was used as the internal standard.After adding 20% perchloric acids to plasma samples, precipitating and centrifugating,plasma samples were separated on a XDB C18 column (150×4.6mm,5μm), with the mobile phase consisted of acetonitrilemethanol20 mmol#8226;L-1 KH??2PO??4 (15∶15∶70,v∶v∶v) .The fluorescence detection wave length was λex=342 nm，λem=420 nm. 　　Results The calibration curves was linear over the concentration ranged of 10.80 to 1296ng#8226;ml-1(r=0.9987),The average relative recovery was 95.62%~107.7%,RSD was 1.4%~2.5%. The extraction recovery was 2.3%~6.4%.Intraand interday precision ranged from 1.4 to 2.5 and 2.8 to 4.3%respectively. 　　Conclusion The method was sensitive，rapid and accurate and could be used in the monitoring of therapeutic drugs and human pharmocokinetic study of tosufloxacin. 　　【Key words】HPLC;tosufloxacin;plasma 　　 　　妥舒沙星属于第4代喹诺酮类抗生素，具有抗菌谱广、抗菌活性强的特点，尤其对需氧革兰阳性球菌和厌氧菌的作用较强。目前在临床上妥舒沙星主要用于治疗呼吸道、胆道、皮肤软组织、耳鼻喉和口腔等感染［1］但有关妥舒沙星血药浓度测定的报道较少［2，3］，且普遍存在测定灵敏度低、最低定量下限较高的弊端。笔者建立高效液相色谱荧光法测定健康人血浆中妥舒沙星的药物浓度分析方法，发现该方法操作简单、快速、灵敏度高，结果准确，可用于妥舒沙星人体血药浓度测定及药动学研究。 　　 　　 材料与方法 　　 　　1.药品与仪器①仪器：Agilent 1200高效液相色谱仪(美国Agilent)；AG285分析天平（瑞士Mettler Tole