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目的建立HPLC-MS/MS法同时测定人血浆中舒尼替尼及其活性代谢产物N-去乙基舒尼替尼(SU12662)的浓度。方法以氘代舒尼替尼为内标,用一步沉淀蛋白法对血浆中舒尼替尼及其活性代谢产物SU12662进行提取。色谱柱Agilent ZORBAX Extend C18(2.1 mm×75 mm×3.5μm),水相0.1%甲酸,有机相95%乙腈进行梯度洗脱,通过电喷雾离子源以正离子多反应监测模式进行检测。考察该方法的专属性、标准曲线和定量下限、精密度和回收率、稳定性、基质效应。结果舒尼替尼在0.5~200 ng·m L-1内呈良好的线性关系(r=0.998 7),定量下限为0.5 ng·m L-1,准确度为0.57%~2.87%,回收率在92.75%~98.62%,日内、日间精密度分别为0.91%~1.92%和5.40%~7.87%。SU12662在0.25~100 ng·m L-1内呈良好的线性关系(r=0.999 9),定量下限为0.25 ng·m L-1,准确度为-2.08%~2.80%,回收率在96.23%~101.12%,日内、日间精密度分别为0.46%~2.46%和5.84%~9.75%。结论该方法简便快速,准确度高,灵敏度好,专属性强,适用于人血浆中舒尼替尼和N-去乙基舒尼替尼浓度的测定。
OBJECTIVE To establish a HPLC-MS / MS method for the simultaneous determination of sunitinib and its active metabolite N-des-ethyl sunitinib (SU12662) in human plasma. Methods Sunitinib deuteride was used as an internal standard, and sunitinib and its active metabolite SU12662 in plasma were extracted by one-step precipitation method. The Agilent ZORBAX Extend C18 column (2.1 mm × 75 mm × 3.5 μm) was used. The column was eluted with 0.1% formic acid in water phase and 95% acetonitrile in organic phase. The electrospray ionization was used to detect positive ions in multiple reaction monitoring mode. Investigate the specificity of this method, the standard curve and lower limit of quantitation, precision and recovery, stability, matrix effects. Results Sunitinib had a good linearity (r = 0.998 7) in the range of 0.5 ~ 200 ng · m L-1 with a lower limit of quantification of 0.5 ng · m L-1 with an accuracy of 0.57% -2.87%. The recovery At 92.75% ~ 98.62%, the intra-day and inter-day precision were 0.91% ~ 1.92% and 5.40% ~ 7.87%, respectively. The linear range of SU12662 was 0.25 ~ 100 ng · m L-1 (r = 0.999 9), the lower limit of quantification was 0.25 ng · m L-1, the accuracy was -2.08% ~ 2.80% and the recovery was 96.23% ~ 101.12%, the intra-day and inter-day precision were 0.46% ~ 2.46% and 5.84% ~ 9.75%, respectively. Conclusion The method is simple and rapid, accurate, sensitive and specific. It is suitable for the determination of sunitinib and n-dethyl sunitinib in human plasma.