高效液相色谱法测定二甲苯磺酸拉帕替尼片有关物质

Determination of Related Substances in Lapatinib Ditosylate Tablets by HPLC

目的建立测定二甲苯磺酸拉帕替尼片有关物质的高效液相色谱法。方法采用Waters Xterra MS C18色谱柱(4.6mm×250 mm,5μm);以0.01 mol.L-1磷酸二氢钠溶液(用磷酸调节pH值至3.2)为流动相A,以乙腈为流动相B,梯度洗脱,流速1.0 mL.min-1;检测波长265 nm,柱温40℃。结果拉帕替尼杂质A、拉帕替尼杂质2和拉帕替尼杂质1分别在0.02～8.08、0.02～8.26和0.02～8.29 mg.mL-1内线性关系良好,r≥0.999 9,定量限分别为1.0、1.4、2.1 ng,杂质高、中、低浓度的平均回收率(n=9)在100.2%～102.9%,RSD(n=9)在0.02%～0.66%,可以满足杂质分析的要求。结论本方法简便、准确、专属性强,可定量测定二甲苯磺酸拉帕替尼片的有关物质。

OBJECTIVE To establish a determination method of the related substances of lapatinib ditosylate tablets by HPLC. METHODS Waters Xterra MS C18 column （4. 6 mm × 250 mm, 5 μm） was selected; 0. 01 mol . L^-1 sodium dihydrogen phosphate solution （pH adjusted to 3.2 with phosphoric acid） was mobile phase A, aeetonitrile was mobile phase B, and gradient elutiun was used at a flow rate of 1.0 mL . min^-1. The detection wavelength was set at 265 nm, and the column temperature was 40 ℃. RESULTS Lapatinib Impurity A, LAPA-2 and LAPA-1 had good linearity in the range of 0.02 - 8.08, 0.02 - 8.26 and 0.02 - 8.29 mg . m^L-1 , respectively （ r ≥ 0. 999 9）. The limits of quantitation （LOQ） were 1.0, 1.4, and 2. 1 ng, respectively. The average recovery （n=9） was in the range of 100.2% - 102.9%, and RSDs （n=9） were in the range of 0.02% - 0.66%. CONCLUSION The method is simple, accurate, and specific and can quantitatively determine the related substances of lapatinib ditosylate tablets.