UPLC测定类鼻疽患者碳青霉烯类抗菌药物血药浓度及其个体给药方案的优化

UPLC detection of blood concentrations of carbapenem antibiotics and optimization of individual drug administration in patients with melioidosis infection

目的采用超高效液相色谱(UPLC)方法检测海南省类鼻疽患者碳青霉烯类抗菌药物亚胺培南和美罗培南的血药浓度,并结合碳青霉烯类抗菌药物的f%T>MIC计算模型优化该类患者抗感染个体给药方案。方法4例类鼻疽患者使用碳青霉烯类抗菌药物达稳态后,取用药前30 min和3 h的血样,采用甲醇沉淀蛋白和二氯甲烷萃取的外标UPLC法测定血药浓度,采用E-Test法测定相应的最低抑菌浓度,运用Excel软件计算f%T>MIC,从而评价类鼻疽患者碳青霉烯类抗菌药物的药效达标情况。结果亚胺培南和美罗培南在0.5~200.0μg/mL内线性良好(R2=0.995和0.993)。亚胺培南和美罗培南的提取回收率为(82.70±9.14)%和(92.86±4.50)%,方法回收率为(90.92±4.63)%和(98.48±2.95)%,日内相对标准偏差为2.99%和11.40%,日间相对标准偏差为2.00%和13.87%。4例类鼻疽患者中,1例出现f%T>MIC不达标情况,经计算调整治疗方案后疗效改善。结论成功建立碳青霉烯类抗菌药物血药浓度测定的方法学,结合f%T>MIC计算模型为海南省类鼻疽患者提供个体化给药方案具有一定的临床指导意义。

Objective To detect the blood concentrations of carbapenem antibiotics imipenem and meropenem by ultra-high performance liquid chromatography(UPLC)in the patients with melioidosis in Hainan Province,and establish f%T>MIC computational model of carbapenem antibiotics for optimizing anti-infection treatment.Methods Blood samples of four patients with melioidosis were collected at 30 minutes and 3 hours before administration of carbapenem antibiotics in steady status.The blood concentration was determined by external standard UPLC method with methanol precipitation protein and dichloromethane extraction.The corresponding minimal inhibitory concentration was measured by E-Test assay.The Excel software was used to calculate f%T>MIC,which could evaluate the efficacy of carbapenem antibiotics in the patients with melioidosis.ResultsThe linear of imipenem and meropenem ranged from 0.5 to 200.0μg/mL was good(R2=0.995 and 0.993).The extraction recovery,method recovery,intra-run relative standard deviation and inter-run relative standard deviation of imipenem and meropenem were(82.70±9.14)%and(92.86±4.50)%,(90.92±4.63)%and(98.48±2.95)%,2.99%and 11.40%and 2.00%and 13.87%,respectively.Of 4 cases with melioidosis,one case was below the standard of f%T>MIC,but the curative effect was improved after adjusting the treatment regimen.Conclusion The methodology for the determination of blood concentrations of carbapenem antibiotics has been successfully established,and f%T>MIC computational model could provide individualized anti-infection treatment for the patients with melioidosis in Hainan province.