用LC-MS/MS法同时测定血清中维奈托克、伏立康唑和阿糖胞苷的血药浓度  

Determination of serum concentrations of venetoclax,voriconazole and cytarabine by LC-MS/MS

作　　者：徐尔高 童娟 魏伟[1] 杨昭毅[1,3] XU Er-gao;TONG Juan;WEI Wei;YANG Zhao-yi(Key Laboratory of Anti-inflammatory and Immune Drugs,Ministryof Education,Institute f Clinical Pharmacology of Chinese Anhui Medical University,1Hefei 230032,Anhui Province,China;Department of Hematology,Provincial Hospital Affiliated to Anhui Medical University,Hefei 230001,Anhui Province,China;Department of Pharmacy,Provincial Hospital Affiliated to Anhui Medical University,Hefei 230001,Anhui Province,China)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,安徽合肥230032 [2]安徽医科大学附属省立医院血液内科,安徽合肥230001 [3]安徽医科大学附属省立医院药学部,安徽合肥230001

出　　处：《中国临床药理学杂志》2023年第20期2995-2999,共5页The Chinese Journal of Clinical Pharmacology

基　　金：“十四五”省级医疗卫生重点专科建设基金资助项目[2021szdzk03临床药学(优先发展)]。

摘　　要：目的 建立一种高效液相色谱-质谱(HPLC-MS/MS)法同时检测人血清中维奈托克、伏立康唑、阿糖胞苷的药物浓度,拟应用于人体药代动力学试验生物样本的测定。方法 用蛋白沉淀法进行血浆样本前处理,Kinetex C18液相色谱柱(2.1 mm×50.0 mm, 2.6μm),A相为3 mmol·L^(-1)甲酸铵+0.1%甲酸水溶液,B相为0.1%甲酸的甲醇溶液,流速0.3 mL·min^(-1),梯度洗脱;在正离子模式下,多反应监测模式扫描监测维奈托克m/z 868.3→636.2和navitoclax m/z 974.4→742.4、伏立康唑m/z 350.2→281.1和氟康唑m/z 307.1→238.3、阿糖胞苷m/z 244.1→112.1和阿昔洛韦m/z 226.1→152.0。结果 该方法中维奈托克、阿糖胞苷、伏立康唑分别在2~5 000 ng·mL^(-1)、2~2 000 ng·mL^(-1)、5~2 000 ng·mL^(-1)线性关系良好,定量下限分别为2 ng·mL^(-1)、2 ng·mL^(-1)、5 ng·mL^(-1)。批内和批间精密度%CV分别为1.50%~14.82%和1.29%~7.16%,平均准确度偏差在90.33%~108.14%,提取回收率%CV在91.91%~110.81%。结论 本研究开发的LC-MS/MS方法有很高的专属性和灵敏度,可用于维奈托克、阿糖胞苷、伏立康唑的临床血药浓度测定。Objective A high-performance liquid chromatographymass spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination venetoclax,voriconazole cytarabinebine in human serum,which was intended to be used in the determination of human pharmacokinetic biological samples.Methods Plasma samples were pretreated with a protein precipitation method on a Kinetex C18liquid chromatography column (2.1 mm×50.0 mm,2.6μm),with 3mmol·L^(-1)ammonium formate+0.1%formic acid aqueous solution in phase A and 0.1%formic acid in methanol solution in phase B,flow rate0.3 m L·min^(-1),gradient elution;in positive ion mode,the multireaction monitoring mode scans monitored venetoclax m/z 868.3→636.2and navitoclax m/z 974.4→742.4,voriconazole m/z 350.2→281.1,fluconazole m/z 307.1→238.3,cytarabine m/z 244.1→112.1 and acyclovir m/z 226.1→152.0.Results The linear relationships among venetoclax,cytarabine and voriconazole were 2-5 000 ng·m L^(-1),2-2 000 ng·m L^(-1),5-2 000 ng·m L^(-1),respectively.The lower limits of quantification were 2 ng·m L^(-1),2 ng·m L^(-1),5 ng·m L^(-1),respectively.The precision%CV was 1.50%-14.82%in batch and 1.29%-7.16%in inter-batch,the average accuracy deviation was 90.33%-108.14%,and the extraction recovery%CV was 91.91%-110.81%.Conclusion The specificity and sensitivity of this method are particularly high,and can be used for clinical determination of venetoclax,cytarabine and voriconazole.

关 键 词：维奈托克 伏立康唑 阿糖胞苷 血清 高效液相色谱-串联质谱 血药浓度检测 

分 类 号：R971[医药卫生—药品]