基于高效液相色谱法检测儿童血液疾病患者血清中伏立康唑浓度及临床应用  

Determination of voriconazole concentration in serum of children with blood diseases by high⁃performance liquid chromatography and its clinical application

作　　者：钟莉莉[1] 陈君[1] 王榆雅 吴琼诗[1] 王敏[1] ZHONG Lili;CHEN Jun;WANG Yuya;WU Qiongshi;WANG Min(Dept.of Pharmacy,Hainan General Hospital&Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,Hainan,China)

机构地区：[1]海南省人民医院/海南医学院附属海南医院药学部,海南海口570311

出　　处：《武汉大学学报（医学版）》2024年第6期688-692,共5页Medical Journal of Wuhan University

基　　金：海南省科协青年科技英才学术创新计划项目(编号:QCXM201923)。

摘　　要：目的:建立一种人血清伏立康唑(VRC)血药浓度高效液相测定法,能快速、准确、稳定为儿童血液疾病患者监测伏立康唑血药浓度,为指导临床用药奠定基础。方法:采用反相-HPLC法,色谱柱为Eclipse XDB-C18柱,4.6 mm×150 mm,5μm。流动相:甲酸铵水溶液(pH 4.0)∶乙腈=66:34;流速:1.0 mL/min;波长:256 nm;Waters Sep-Pak C18固相萃取小柱对血样进行预处理。结果:VRC和内标峰保留时间分别为9.7 min和11.0 min,分离良好,血样中内源性物质无干扰;回归方程Y=0.295 3X-0.004 3,R2=0.999,血清中VRC线性范围为0.10~19.87μg/mL,定量下限为0.10μg/mL;准确度、精密度、稳定性RSD均<5%。对6名患者进行了血样监测。结论:伏立康唑血药浓度在儿童中个体差异大,对儿童血液疾病患者开展治疗药物监测,有助于提高临床疗效,减少不良反应的发生风险。本方法操作简便,结果准确,适用于临床中伏立康唑的治疗药物监测。Objective:To establish a high‑performance liquid chromatography(HPLC)method for the determination of voriconazole(VRC)in human serum,which can rapidly,accurately,and stably monitor the concentration of voriconazole in children with blood diseases and lay a foundation for guiding clinical drug use.Methods:Reverse phase HPLC method was used(Chromatographic column:Eclipse XDB‑C18 column,4.6 mm×150 mm,5μm.Mobile phase:Ammonium formate aqueous solution(pH 4.0)∶acetonitrile=66∶34;Flow rate:1.0 mL/min;Wavelength:256 nm).The blood samples were pretreated with Waters Sep Pak C18 solid phase extraction column.Results:The retention time of VRC and internal standard peaks was 9.7 min and 11.0 min,respectively,with good separation and without interference from endogenous substances in blood samples.A regression equation was Y=0.2953X-0.0043,R²=0.999,the linear range of VRC in serum was 0.10‑19.87μg/mL,the lower limit of quantification was 0.10μg/mL;RSDs of accuracy,precision and stability were<5%.Blood samples were monitored in 6 patients.Conclusion:The concentration of voriconazole in the blood varies significantly among children.Monitoring therapeutic drugs in children with blood diseases is helpful to improve clinical efficacy and reduce the risk of adverse reactions.This method is simple,accurate,and suitable for clinical monitoring of voriconazole.

关 键 词：伏立康唑 高效液相色谱法 治疗药物监测 儿童 血液肿瘤 

分 类 号：R969.1[医药卫生—药理学]