Qualitative Analysis of an Unknown Impurity in Terbinafine Hydrochloride Cream by Heart-cutting 2D-LC-MS and Determination of Its Correction Factor

OBJECTIVE To establish a method of heart-cutting two-dimensional liquid chromatography coupled with Quadrupole time-of flight mass spectrometry(2D-LC-Q/TOF) to identify an impurity with relative retention time(RRT) of 0.4 in terbinafine hydrochloride cream and determine its correction factor. METHODS One-dimensional chromatographic conditions were as listed. A Diamonsil C₁₈ was used, and 0.2% triethylamine buffer(adjust pH to 7.5 with glacial acetic acid)-methanol-acetonitrile (30:42:28) as the mobile phase A, and triethylamine buffer-methanol-acetonitrile(5:57:38) as the mobile phase B, in gradient mode, at a flow rate of 0.8 mL·min^-1. The detection wavelength was set at 280 nm. Two-dimensional chromatographic conditions were as listed. A Tsk gel ODS 100 V was used, with 0.1% formic acid solution-methanol(20:80) as the mobile phase, APCI source was used at positive ion detection mode. The correction factor of the detected impurity was determined in the one-dimensional chromatographic system. RESULTS According to the qualitative results of mass spectrometry and the comparison of reference substance, the RRT 0.4 impurity in terbinafine hydrochloride cream was confirmed as the process impurity, which could provide the basis for the improvement of subsequent refining process. The correction factor of the impurity was 0.21 compared with terbinafine, which suggested that the method of self-control of main component with correction factor was more reasonable. CONCLUSION The 2D-LC-MS method can be used to identify weak polarity impurities in terbinafine hydrochloride cream, which provides ideas for the research of other weak polarity impurities in terbinafine hydrochloride cream and impurities of the similar preparations with complex matrix, and it is also an effect technology to control the quality of terbinafine hydrochloride cream.