Kinowski J M, Bressolle F, Fabre D, Goncalves F, Rouzier-Panis R, Galtier M
Laboratoire de Pharmacocinétique, Hôpital Carémeau, Nîmes, France.
J Pharm Sci. 1994 May;83(5):736-41. doi: 10.1002/jps.2600830529.
An HPLC method with UV detection was developed for the analysis of ceftibuten (cis-isomer) and its metabolite (trans-isomer of ceftibuten) in plasma and urine. The detection was performed at 254 nm. The procedure for the plasma assay involves the addition of an internal standard (ceftazidime), followed by treatment of the samples with acetonitrile and dichloromethane. The urine samples, after dilution (10- to 40-fold), were analyzed by a column-switching technique without internal standard. The proposed technique is reproducible, selective, reliable, and sensitive. Linear detector responses were observed for the calibration curve standards in the ceftibuten conentration range of 0.10 to 20 mg/L for plasma and 0.10 to 50 mg/L for urine, and in the metabolite concentration range of 0.20 to 4 mg/L for plasma and 0.20 to 16 mg/L for urine. The limit of quantitation is 0.1 mg/L for ceftibuten and 0.2 mg/L for the transisomer in plasma and urine. The reproducibility of the analytical method according to the statistical coefficients is approximately 7%. The accuracy of the method is good; that is, the relative error is < 5%. The methods were applied to pharmacokinetic studies of ceftibuten after multiple oral administration (400 mg every 12 h for 8 days) to healthy volunteers.
建立了一种采用紫外检测的高效液相色谱法，用于分析血浆和尿液中的头孢布烯（顺式异构体）及其代谢物（头孢布烯反式异构体）。检测在254nm波长下进行。血浆分析步骤包括加入内标（头孢他啶），然后用乙腈和二氯甲烷处理样品。尿液样品经稀释（10至40倍）后，采用柱切换技术进行分析，无需内标。所提出的技术具有可重复性、选择性、可靠性和灵敏性。在血浆中头孢布烯浓度范围为0.10至20mg/L、尿液中为0.10至50mg/L，以及血浆中代谢物浓度范围为0.20至4mg/L、尿液中为0.20至16mg/L时，校准曲线标准品的检测器响应呈线性。血浆和尿液中头孢布烯的定量限为0.1mg/L，反式异构体的定量限为0.2mg/L。根据统计系数，分析方法的重现性约为7%。该方法的准确性良好，即相对误差<5%。这些方法应用于健康志愿者多次口服给药（每12小时400mg，共8天）后头孢布烯的药代动力学研究。
