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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。
Objective To establish a LC-MS / MS method for determining the concentration of lapatinib in the plasma and tumor tissues of tumor-bearing mice. Methods Plasma and tumor samples were determined by injection of methanol precipitated protein and gefitinib as internal standard. The mobile phase was methanol-water (containing 2 nmol·L-1 ammonium acetate and 0.1% formic acid) (90:10) at a flow rate of 0.4 m L Min-1, column temperature 40 ℃, injection volume 20μL, total analysis time 3 min. Electrospray ionization mass spectrometry was used for mass spectrometry analysis in multiple reaction ion monitoring mode. Results The linear range of lapatinib in blood and tumor tissues was 25 ~ 25 000 μg · L -1 and 1 ~ 2000 μg · L -1, respectively. The intra-assay RSD was ≤1.4% and 8.3%, respectively. Inter-assay RSD was ≤ 3.7% and 7.8%, respectively. The extraction recovery rates ranged from 99.4% to 102.3% and from 87.7% to 94.1%, respectively. The matrix effects ranged from 85% to 115%. Conclusion The method is sensitive, accurate and rapid, and suitable for determining the concentration of lapatinib after oral administration.