妥舒沙星人體血藥濃度測定及藥代動力學研究

【摘要】 目的 建立反相高效液相色譜熒光檢測法測定人血漿中妥舒沙星濃度的方法。方法以加替沙星為內標，血漿經酸化采用20%高氯酸提取，色譜柱為XDB C18柱（4.6 mm×150 mm，5 μm）；流動相為乙腈甲醇20 mmol#8226;L-1磷酸二氫鉀（15∶15∶70），熒光檢測(λex=342 nm，λem=420 nm)。結果 妥舒沙星血漿濃度在10.80~1296 ng#8226;ml-1內具有良好線性關系，平均相對回收率大于95%，萃取回收率大于60%，日內、日間相對標準差（RSD）均小于4.3%。結論該方法靈敏、準確，可用于妥舒沙星的藥動學研究。

【關鍵詞】 高效液相色譜熒光法；妥舒沙星；血漿

文章編號：1003-1383(2010)06-0675-04 中圖分類號：R 927.2 文獻標識碼：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

妥舒沙星屬于第4代喹諾酮類抗生素，具有抗菌譜廣、抗菌活性強的特點，尤其對需氧革蘭陽性球菌和厭氧菌的作用較強。目前在臨床上妥舒沙星主要用于治療呼吸道、膽道、皮膚軟組織、耳鼻喉和口腔等感染［1］但有關妥舒沙星血藥濃度測定的報道較少［2，3］，且普遍存在測定靈敏度低、最低定量下限較高的弊端。筆者建立高效液相色譜熒光法測定健康人血漿中妥舒沙星的藥物濃度分析方法，發現該方法操作簡單、快速、靈敏度高，結果準確，可用于妥舒沙星人體血藥濃度測定及藥動學研究。

材料與方法

1.藥品與儀器①儀器：Agilent 1200高效液相色譜儀(美國Agilent)；AG285分析天平（瑞士Mettler Toledo公司)；MS1 Minishaker 渦旋振蕩儀(廣州科儀實驗室技術有限公司)；Biofuge stratos 高速冷凍離心機(德國heraeus)。②藥品與試劑:妥舒沙星對照品(赤峰萬澤制藥有限責任公司，批號:20070504)；加替沙星(內標，中國藥品生物制品檢定所)。試劑：甲醇、乙睛為色譜純，水為二次蒸餾水，其余試劑均為分析純。……