RESUMO
@#This study aimed to identify the related substances of lorazepam tablets by liquid chromatography mass spectrometry (LC-MS). To separate the related substances of lorazepam tablets, gradient elution was performed using acetonitrile and 0.1% acetic acid -20 mmol/L of ammonium acetate as mobile phase on Inert Sustain C18 (250 mm × 4.6 mm, 5 μm).The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry (ESI-Q-TOF/MS).The structures of the related substances were identified by spectral analysis. Under the established analytical condition, lorazepam and its related substances were adequately separated, and 22 major related substances with content greater than 0.1% were detected and identified by hyphenated techniques in lorazepam tablets and their stressed samples.Among them, 5 were the impurities listed in the USP or EP, and the others were unknown related substances identified for the first time in this paper.The LC-MS technique can effectively separate and identify the related substances of lorazepam tablets, which provides some reference for quality control.
RESUMO
OBJECTIVE: To evaluate the process control capability of lorazepam tablets produced in China. METHODS: Near-infrared spectroscopy combined with cluster analysis(CLA) and principal component analysis(PCA) were used to characterize the different processes and process control space of lorazepam tablets produced in China. Universal quantitative model was built to obtain the content predictions of individual units(tablets), on base of which process mean value,intra-batch and inter-batch differences and distribution status were calculated by univariate statistics analysis methods. RESULTS: Three different manufacturing processes of lorazepam tablets were characterized by both CLA and PCA. The process control spaces reconstructed by the second and third principal components indicated that the process of manufacturer B had smaller variation than that of manufacturer A. The universal quantitative model had a principal component number of 5, r2 square value of 93.89% and bias of -0.008 56. The statistic distribution of API contents showed that 9 batches out of the total 27 batches had relative lager intra-batch differences and manufacturer B had better inter-batch differences than manufacturer A. CONCLUSION: The method this study established can reveal the control levels of different processes of lorazepam tablets, which provide an efficient quality consistency evaluation means for generic drug consistency assessment.
