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AML患者血浆中维奈克拉、白消安和伏立康唑浓度测定方法的建立与应用
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| 篇名： | AML患者血浆中维奈克拉、白消安和伏立康唑浓度测定方法的建立与应用 |
| TITLE： | Establishment and application of a determination method for plasma concentrations of venetoclax，busulfan and voriconazole in patients with acute myeloid leukemia |
| 摘要： | 目的 建立同时测定急性髓系白血病（AML）患者血浆中维奈克拉、白消安和伏立康唑浓度的方法并应用于临床。方法血浆样品经乙腈沉淀蛋白后，分别以维奈克拉-D8、白消安-D8、泊沙康唑为内标，采用液相色谱-串联质谱（LC-MS/MS）法检测。以PhenomenexKinetex®C18为色谱柱，以0.1%甲酸溶液（含2mmol/L乙酸铵）-0.1%甲酸乙腈溶液为流动相进行梯度洗脱；流速为0.8mL/min；柱温为40℃；进样量为5μL；运行时间为3.10min；采用电喷雾离子源，以多反应监测方式进行正离子扫描，用于定量分析的离子对包括m/z868.4→636.3（维奈克拉）、m/z264.1→151.1（白消安）、m/z350.1→224.0（伏立康唑）等。采用上述LC-MS/MS法测定10例联合用药AML患者体内维奈克拉、伏立康唑的血药浓度和5例行异基因造血干细胞移植预处理患者体内白消安的血药浓度。结果维奈克拉、白消安、伏立康唑检测质量浓度的线性范围分别为50～10000、15～3000、50～10000ng/mL（R2≥0.9990），定量下限分别为50、15、50ng/mL；3种待测药物的日内、日间精密度的RSD均低于10%，准确度（相对误差）为－10.00%～12.96%；平均提取回收率为92.54%～100.95%，平均基质效应为89.98%～101.49%，稀释可靠性可覆盖试验样品所用的稀释倍数，稳定性试验的相对误差绝对值均不高于16.25%。纳入患者体内维奈克拉、白消安、伏立康唑的血药浓度分别为496.20～4250.45、233.48～2002.28、475.51～5710.18ng/mL。结论所建LC-MS/MS法快速、灵敏、操作简便，可用于AML患者维奈克拉、白消安和伏立康唑血药浓度治疗药物监测。 |
| ABSTRACT： | OBJECTIVE To establish a method for simultaneous determination of venetoclax， busulfan and voriconazole in plasma of patients with acute myeloid leukemia （AML）， and apply it clinically. METHODS Plasma samples were subjected to protein precipitation using acetonitrile and subsequently analyzed by liquid chromatography-tandem mass spectrometry （LC-MS/MS） using venetoclax-D 8 ， busulfan-D 8 and posaconazole as internal standards. The separation was performed on a Phenomenex Kinetex ® C 18 column with a mobile phase composed of 0.1% formic acid solution （2 mmol/L ammonium acetate）-0.1% formic acid in acetonitrile （gradient elution） at a flow rate of 0.8 mL/min. The column temperature was set at 40 ℃， the sample size was 5 μL， and the total run time was 3.10 min. An electrospray ionization source was employed， and positive ion scanning was conducted using multiple reaction monitoring mode. The ion pairs used for quantitative analysis included m/z 868.4→636.3 （venetoclax）， m/z 264.1→151.1 （busulfan）， and m/z 350.1→224.0 （voriconazole）. The above LC-MS/MS method was adopted to determine plasma concentrations of venetoclax and voriconazole in 10 AML patients， as well as plasma concentration of busulfan in 5 patients undergoing conditioning treatment for allogeneic hematopoietic stem cell transplantation. RESULTS The linear ranges of venetoclax， busulfan and voriconazole were 50-10 000， 15-3 000 and 50-10 000 ng/mL， respectively （ R 2 ≥0.999 0）， with lower limits of quantification of 50， 15 and 50 ng/mL， respectively. The RSDs of intra-day and inter-day precision tests for all three analytes were all less than 10%， with accuracy （relative errors） ranging from －10.00% to 12.96%. The average extraction recovery ranged from 92.54% to 100.95%， and the average matrix effect was 89.98%-101.49%. Dilution reliability covered all dilution factors used in the test samples， and the absolute values of relative errors in stability tests were all≤16.25%. The plasma concentrations of venetoclax， busulfan and voriconazole in enrolled patients were 496.20-4 250.45， 233.48-2 002.28 and 475.51-5 710.18 ng/mL， respectively. CONCLUSIONS The LC-MS/MS method established in this study is rapid， sensitive and easy to operate， and can be used for the therapeutic drug monitoring of venetoclax， busulfan and voriconazole. |
| 期刊： | 2026年第37卷第10期 |
| 作者： | 张振华；张梦茹；郭傲翔；陈卉；乡世健；周本杰；葛冰琛 |
| AUTHORS： | ZHANG Zhenhua，ZHANG Mengru，GUO Aoxiang，CHEN Hui，XIANG Shijian，ZHOU Benjie，GE Bingchen |
| 关键字： | 维奈克拉；白消安；伏立康唑；急性髓系白血病；液相色谱-串联质谱法；治疗药物监测 |
| KEYWORDS： | venetoclax； busulfan； voriconazole； acute myeloid leukemia； LC-MS/MS； therapeutic drug monitoring |
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