摘要
目的建立测定荷瘤小鼠血浆和肿瘤组织中拉帕替尼浓度的LC-MS/MS法。方法血浆和肿瘤组织样品采用甲醇沉淀蛋白后进样测定,以吉非替尼为内标。色谱柱:Agilent Eclipse XDB-C18(150 mm×2.1 mm,5 mm),流动相:甲醇-水(含2 nmol·L-1醋酸铵和0.1%甲酸)(90∶10),流速0.4 m L·min-1,柱温40℃,进样量20μL,总分析时间3 min。质谱采用电喷雾离子源,以多反应离子监测模式进行定量分析。结果拉帕替尼在血和肿瘤组织中的线性范围分别为25~25 000μg·L-1和1~2 000μg·L-1;批内RSD分别≤1.4%和8.3%,批间RSD分别≤3.7%和7.8%;提取回收率分别为99.4%~102.3%和87.7%~94.1%;基质效应均在85%~115%内。结论本方法灵敏度高,准确、快速,适于测定拉帕替尼口服后到达肿瘤组织的浓度。
AIM To develop an LC-MS /MS method for determination of lapatinib concentrations in the plasma and tumor tissues of tumor-bearing mice. METHODS The analytes and the internal standard( IS,gefitinib) were extracted from 100 μL aliquots of plasma and tumor homogenate by methanol precipitation. Chromatographic separation was achieved on an Agilent Eclipse XDB C18column( 150 mm × 2. 1 mm,5 μm) in a run time of 3 min with the mobile phase consisted of methanol and water( containing 2 nmol·L-1ammonium acetate and 0.1% formic acid) at the ratio of( 90∶ 10),which was pumped at a flow rate of 0. 4 m L·min-1. The column temperature was set for 40℃ and the injection volume was 20 μL. Detection of analytes and IS was done by tandem mass spectrometry,operated in positive ion and multiple reaction monitoring( MRM) mode. RESULTS The liner range of lapatinib in mice plasma and tumor tissues was 25-25 000 μg·L-1and 1-2 000 μg·L-1,respectively. The intra-batch RSD was less than 1. 4% and 8. 3% respectively,and the inter-batch RSD was less than 3. 7%and 7. 8% respectively. The extraction recoveries were 99. 4%-102. 3% and 87. 7%-94. 1%,respectively. The matrix effects were all within 85%-115%. CONCLUSION The method is sensitive,accurate and fast,and suitable for the determination of lapatinib concentrations in tumor tissues after oral administration.
出处
《中国临床药学杂志》
CAS
2015年第3期153-158,共6页
Chinese Journal of Clinical Pharmacy
