HPLC法测定人血浆中比阿培南浓度及其药动学研究.docVIP

HPLC法测定人血浆中比阿培南浓度及其药动学研究 　　[摘要] 目的：建立人血浆中比阿培南的高效液相色谱检测方法。方法：色谱柱为Agilent ZORBAX Bonus-RP （4.6 mm×250 mm，5 μm）；流动相为甲醇和0.03%醋酸水溶液，采用梯度洗脱法；流速为1.00 ml/min；检测波长为300 nm，血浆样品处理选用5-羟基吲哚乙酸为内标，采用硫酸锌沉淀蛋白。结果：比阿培南在0.2～50.0 μg/ml范围内线性良好，HPLC测定定量下限为0.2 μg/ml，比阿培南和内标在血浆的保留时间分别为3.9 min和9.7 min，出峰迅速。比阿培南浓度分别为0.5、5.0和40.0 μg/ml，血浆样本回收率分别为101.8%、100.8%、100.4%；精密度试验日内和日间RSD均小于15%，稳定性试验结果表明血浆样品在样品处理过程中较稳定（RSD 　　[关键词] 比阿培南；高效液相色谱法；梯度洗脱 　　[中图分类号] R927.2 [文献标识码] A [文章编号] 1673-7210（2011）12（b）-075-03 　　 　　Studies on the concentration and bioequivalence of the Biapenem in human plasma by HPLC 　　ZHANG Aili, LAN Ting, LI Muqiong, ZHANG Junna , LI Xiaoye 　　Department of Chemistry, School of Pharmacy, the Fourth Military Medical University, Shaanxi Province, Xi′an 710032, China 　　[Abstract] Objective: To establish a method for the determination of Biapenem in human plasma by HPLC. Methods: Agilent ZORBAX Bonus-RP (4.6 mm×250 mm, 5 μm) was used as the analytical column; mobile phase was composed of methanol-0.03% acetic acid solution (gradient elution); the flow rate was 1.00 ml/min; the UV detection was carried out at 300 nm. The plasma samples were performed by protein precipitation with ZnSO4 using 5-hydroxyindole acetic acid as internal standard sample. Results: The assay was linear over the concentration range of 0.2-50.0 μg/ml for Biapenem in human plasma. The limit of quantitation for biapenem was 0.2 μg/ml. The retention time of Biapenem and internal standard sample in plasma was 3.9 min and 9.7 min, respectively. The recovery rate at concentrations of 0.5, 5.0, 40.0 μg/ml were 101.8%,100.8%,100.4%, respectively. The method was accurate with all intra-day and inter-day mean concentrations within 15% of nominal values. Furthermore, the stability results showed that Biapenem was stable during sample processing (RSD 　　2.1.5 给药方法 　　临床上本品采用的给药方式为静脉滴注，故本试验采用将注射用比阿培南，并用100 ml 氯化钠注射液稀释，静脉滴注，滴注时间为1.0 h。根据说明书，注射用比阿培南的正常临床治疗剂量为静脉滴注，一次300 mg，12 h一次。故本试验采用低剂量组单次静脉滴注150 mg；中剂量组单次静脉滴