摘要
目的:建立高效液相色谱质谱联用法(LC-MS/MS)测定中原汉族房颤患者血浆中利伐沙班稳态血药浓度。方法:选用UItimate XB-C8(3.0 mm×250 mm,5μm)色谱柱,以0.1%甲酸水(A)-0.1%甲酸乙腈溶液(B)为流动相进行梯度洗脱,流速为0.3 mL·min^-1,柱温为30℃,用电喷雾离子化源,正离子方式,多反应监测(MRM)扫描方式进行监测,用于定量分析的离子反应分别为m/z 436.0(母离子)→m/z 145.1/230.9(利伐沙班),m/z 472.2(母离子)→m/z 289.0/324.1(内标达比加群),考察其专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性,并使用该方法对20例房颤患者稳态谷浓度和峰浓度进行测定。结果:血浆中利伐沙班的标准曲线方程为Y=2.48X+0.04,R2=0.9937(W=1/X2),在质量浓度1~500 ng·mL^-1范围内线性关系良好,定量下限回收率范围在101.0%~119.2%之间,利伐沙班低、中、高浓度质控样品的批内批间准确度在86.8%~116.7%之间,批内批间精密度均低于7.9%;利伐沙班及其内标达比加群的绝对提取回收率分别在85.3%~108.0%,83.2%~88.6%之间,且RSD在3.0%~6.7%之间;利伐沙班、达比加群的基质效应可忽略不计;利伐沙班血浆样品冻融循环3次,-20℃存放的稳定性考察结果均符合原则要求,测得20例中原汉族房颤患者利伐沙班稳态谷质量浓度为(83.86±84.56)ng·mL^-1,测得稳态峰质量浓度为(326.69±156.13)ng·mL^-1。结论:该方法快速、灵敏、准确,专属性强,重复性好,适用于中原汉族房颤患者血浆利伐沙班药物浓度的测定。
Objective:To develop a high performance liquid chromatography-mass spectrometry(LC-MS/MS)method for the determination of the steady-state plasma concentration of rivaroxaban in Chinese Han patients with atrial fibrillation. Methods:The analytes were separated on a UItimate XB-C8 column(3.0 mm×250 mm,5 μm) maintained at 30℃ with a gradient elution of 0.1% formic acid water and 0.1% formic acid acetonitrile solution at a flow rate of 0.3 mL·min^-1. In the positive electrospray ionization mode,quantification was performed using multiple reaction monitoring(MRM)to monitor m/z 436.0(parent ion)→ 145.1/230.9 for rivaroxaban and m/z 472.2(parent ion)→ 289.0/324.1 for internal standard dabigatran. Specificity,standard curve,lower limit of quantification,precision,recovery,matrix effects and stability were examined. Results:The standard curve equation of rivaroxaban in plasma was Y=2.48 X+0.04,R2=0.993 7(W=1/X2),the linear relationship was good in the range of 1-500 ng·mL^-1,and the recovery range of lower limit of quantification between 101.0% and 119.2%,the accuracy of inter-batch rivaroxaban measurement in low,medium,and high-concentration quality control samples was between 86.8% and 116.7%,and the intra-batch precision was below 7.9%;The absolute extraction recoveries of rivaroxaban and dabigatran were 85.3%-108.0% and 83.2%-88.6% respectively,RSDs were between 3.0%-6.7%. The matrix effects of rivaroxaban and dabigatran were negligible. Rivaroxaban plasma concentration remained stable after 3 freeze-thaw cycles and store at-20 ℃ for a long time,this situation meets the principle requirements. The steadystate rivaroxaban valley concentration in 20 patients was measured,the valley concentration was(83.86±84.56)ng·mL^-1 and the peak concentration was(326.69±156.13)ng·mL^-1. Conclusion:This method is fast,sensitive,accurate,specific,and repeatable. It is applied to the determination of rivaroxaban concentration in patients with atrial fibrillation at high risk of embolism,and it also is used to detect the steady-state plasma concentration of rivaroxaban.
作者
袁冬冬
王亚蕾
张寒娟
王高彪
郭丽萍
可钰
YUAN Dong-dong;WANG Ya-lei;ZHANG Han-juan;WANG Gao-biao;GUO Li-ping;KE Yu(Zhengzhou 7th People’s Hospital,Zhengzhou 450016,China;Zhengzhou University,Zhengzhou 450016,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2020年第8期1399-1404,共6页
Chinese Journal of Pharmaceutical Analysis
基金
河南省医学科技攻关计划项目(No.2018020853)。
