Related substances in empagliflozin determined by LC-MS/MS / 国际药学研究杂志

ABSTRACT

Objective To develop a LC-MS/MS method for the quantification of empagliflozin(EPLZ)impurity X(EPLZ-X) in EPLZ pharmaceutical product. Methods Isocratic chromatographic separation was performed on a Thermo BDS C18 column(4.6 mm × 100 mm,2.4mm). The mobile phase consisting of acetonitrile-water(75∶25,V/V)was eluted at a flow rate of 0.7 ml/min. ESI source was applied and operated in the positive ion mode. multiple reaction monitoring(MRM)mode with the transitions of m/z 785→m/z 475 and m/z 785→m/z 418 were used to quantify the EPLZ-X. Results The method was linar in the concentration range from 0.5 to 100.6 ng/ml. The limit of quantification was 0.5 ng/ml. The intra-and inter-day precision values were both below 11.8%,and accuracy was within ±2.5%in all quality control samples. The average recovery was 105.1%、109.8%and 102.6%,respectively. Conclusion The method provides a sensitive and specific means for the determination of EPLZ-X in EPLZ pharmaceutical substances and completely meets the requirement of European Medicines Evaluation Agency(EMEA)(a limit of not more than 60×10-6 g for the mutagenic impurity EPLZ-X).