HPLC-UV method with solid-phase extraction for the quantitative determination of biapenem in human plasma and its application in pharmacokinetic study

固相萃取HPLC-UV法测定人血浆中比阿培南浓度及其药代动力学研究(英文)

Biapenem, a new parenteral carbapenem, has been widely used for treating bacterial infections. A simple, effective and accurate method based on solid-phase extraction （SPE） and HPLC was developed for the quantitative determination of biapenem in human plasma. Stability and feasibility of the method was validated through a series of experiments. Using Vitamin B6 as an internal standard, analyte was separated on a Capcell Pak C18 column after SPE on Oasis hydrophilic-lipophilic balance （HLB） cartridge. The mobile phase was comprised of 0.05 mol/L NaH2PO4 （pH 5.7） and methanol （98：2, v/v） at a flow rate of 1.0 mL/min. Ultraviolet absorbance was measured at 300 nm. The calibration curve was linear in the concentration range of 0.04-50.00 μg/mL, and the lower limit of quantification was as low as 0.04 μg/mL. Recovery rates of biapenem at 0.10, 5.00, and 25.00 μg/mL were about 70%. The validated method has been successfully applied for quantifying biapenem in human samples and a pharmacokinetic study of 12 healthy volunteers who received three different doses （150, 300 and 600 mg） of biapenem by intravenous infusion. Our method has featured good accuracy and precision, and the processed sample was stable. Therefore, it can be propagated for clinical use.

比阿培南是一种新型经胃肠外吸收的碳青霉烯类抗生素，广泛用于治疗多种细菌感染。本试验建立了一种简便、有效、精确的固相萃取HPLC法测定人血浆中比阿培南的浓度。样品和内标物VitaminB。经固相萃取后通过Capcell Pak C18柱进行分离。测定方法以0．05mol/L磷酸二氢钠（pH5．7）-甲醇（98：2，v／v）为流动相，流速为1．0mL／min，检测波长为300nm。比阿培南在0．04-50．00μg／mL浓度范围内线性关系良好，最低定量限可至0．04μg／mL，0．10、5．00和25．00μg／mL三个浓度的提取回收率均在70％左右。这种测定方法成功地应用于12名健康志愿者单次静脉滴注三剂量（150、300和600mg）比阿培南后的药动学研究。本方法具有良好的精密度和准确度，并且保证样品处理后的稳定性，因此能广泛应用于临床研究。