高效液相色谱法测定血浆万古霉素药物浓度及其药物代谢动力学/药物效应动力学临床应用  

Determination of vancomycin drug concentration in plasma by high performance liquid chromatography and clinical application of PK/PD

作　　者：张燕 胡琴 胡凯[3] 张颖帆 黄玲 罗荣耀 黄琪[2] ZHANG Yan;HU Qin;HU Kai;ZHANG Yingfan;HUANG Ling;LUO Rongyao;HUANG Qi(College of Pharmacy,Dali University,Dali 671000,China;Department of Pharmacy,Xiangya Hospital Central South University,Changsha 410008,China;Department of Neurology,Xiangya Hospital Central South University,Changsha 410008,China;Operating Room,Xiangya Hospital Central South University,Changsha 410008,China)

机构地区：[1]大理大学药学院,云南大理671000 [2]中南大学湘雅医院药学部,湖南长沙410008 [3]中南大学湘雅医院神经内科,湖南长沙410008 [4]中南大学湘雅医院手术室,湖南长沙410008

出　　处：《老年医学研究》2023年第2期25-30,共6页Geriatrics Research

摘　　要：目的 建立高效液相色谱法(HPLC)测定万古霉素血药浓度,并结合药物代谢动力学/药物效应动力学(PK/PD)参数调整老年患者给药方案。方法 将含有万古霉素的血浆样品经100μL的10%高氯酸—甲醇—乙腈(2:1:1)混合蛋白处理剂沉淀后,涡旋离心取上清液150μL于内衬管,以乙腈—水(含25 mmol/L磷酸二氢钾,pH=3.2,V/V=8:92)为流动相,流速为0.8 mL/min,色谱柱为Agilent ZORBAX SB-C18 (250 mm×4.6 mm,5μm),柱温为40℃,检测波长为220 nm进行分析。考察方法的专属性、线性、精密度与回收率。同时根据患者多剂量静脉滴注万古霉素达稳态后血药浓度,采用一室模型计算患者输注段和消除段相关PK参数,建立万古霉素AUC_(0~24h)/MIC计算模型,结合患者输注段、消除段血药浓度评价老年患者中AUC_(0~24h)/MIC达标情况。结果 本研究建立的HPLC专属性强,不易受其他药物干扰,几乎无残留。万古霉素血药浓度在1.18~75.80μg/mL范围内线性关系良好,R2=0.999 4;日内、日间精密度(RSD)值均<15%。万古霉素在室温、4℃、-20℃条件下稳定性好,RSD值均<15%。本研究建立了便捷的万古霉素AUC_(0~24h)/MIC计算模型,并将该模型应用于多例老年患者调整用药方案,调整后患者临床指标均好转。结论本研究建立测定万古霉素血药浓度的HPLC符合生物样品测定要求,可用于临床万古霉素血药浓度测定。同时,结合万古霉素AUC_(0~24h)/MIC结果可制定调整患者给药方案。Objective To establish high-performance liquid chromatography(HPLC)method for determining the blood concentration of vancomycin,and to adjust the dosage regimen of elderly patients combined with pharmacokinetics/pharmacodynamics(PK/PD)parameters.Methods After plasma samples containing vancomycin were precipitated with 100μL of 10%perchloric acid-methanol-acetonitrile(2∶1∶1),then was vortex and centrifugation,final getting the 150μL supernatant was taken into the lined tube.The plasma samples containing vancomycin separation and analysis were car⁃ried out on Agilent ZORBAX SB-C18(250 mm×4.6 mm,5μm)at 40℃.The mobile phase was acetonitrile-water(con⁃taining 25 mmol/L potassium dihydrogen phosphate,pH=3.2,V/V=8∶92)at the flow rate of 0.8 mL/min.The detec⁃tion wavelength was 220 nm.The specificity,linearity,precision,and recovery rate of the method were investigated.Ac⁃cording to the blood concentration of patients after muti-dose intravenous infusion vancomycin reached a steady state,and the pharmacokinetic parameters of the infusion segment and elimination segment of patients were calculated.The calcula⁃tion model of vancomycin AUC_(0~24h)/MIC based on pharmacokinetic theory was established by adopting one-compartment model.Then combined with the infusion segment and elimination concentration to assess AUC_(0~24h)/MIC whether up to stan⁃dard in elderly patients.Results The HPLC method established in this study had strong specificity,less possibility in⁃terfered with by other drugs,and almost no residue.The linearity of vancomycin was good in the range of 1.18 to 75.80μg/mL,R2=0.9994.The intra-day and inter-day RSD were less than 15%.Vancomycin had good stability under the con⁃dition of room temperature,4℃and-20℃which RSD was less than 15%.We established a convenient AUC_(0~24h)/MIC cal⁃culation model.The model was used to adjust the medication of many elderly patients in our hospital,and the results showed that all patients clinical index improved after adjusting the medication pla

关 键 词：高效液相色谱法 万古霉素 血药浓度 药物代谢动力学 药物效应动力学 

分 类 号：R969[医药卫生—药理学]