Identification and Source Analysis of Unknown Impurities in the Excipients of Tolterodine Tartrate Tablets by 2D-LC-QTOF-MS Method
Objective To establish an online heart-cutting two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry(2D-LC-QTOF-MS)method for identifying the unknown impurities in the excipients of Tolterodine Tartrate Tablets,and to analyze the sources of impurities.Methods The one-dimensional liquid chromatography was performed on the Waters XBridge-C18 column(250 mm×4.6 mm,5 μm),the mobile phase was acetonitrile-water-perchloric acid(200∶800∶1.5,V/V/V)-acetonitrile(gradient elution),the flow rate was 1.0 mL/min,the detection wavelength was 220 nm,the column temperature was 65℃,the injection volume was 10 μL.The two-dimensional liquid chromatography was performed on the Agilent Poroshell 120 EC-C18 column(100 mm×2.1 mm,2.7 μm),the mobile phase was ammonium formate buffer(20 mmol/L ammonium formate solution,adjusted to pH 3.0 with formic acid)-acetonitrile(55∶45,V/V),the flow rate was 0.3 mL/min,the detection wavelength was 220 nm,the column temperature was 25℃.The electron spray ionization(ESI)was adopted with positive ion detection mode.Results The possible structure of an unknown impurity was identified,and it was confirmed that the impurity was introduced by hydroxypropyl methylcellulose,a film-coated premix in the formulation.The hydroxypropyl methylcellulose of eight manufacturing enterprises was tested,and that of one enterprise was detected.Conclusion This method can be used for online qualitative identification of unknown impurities in Tolterodine Tartrate Tablets.
Tolterodine Tartrate Tabletstwo-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometryheart-cuttingexcipienthydroxypropyl methylcellulose