Evaluation of polysaccharide‐based chiral stationary phases in quality control of (S)‐mirtazapine

High-performance liquid chromatographic methods were developed for separation of the enantiomers of mirtazapine and its four process-related substances. The direct separations were achieved on chiral stationary phases containing amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak® AD-H), cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel® OD-H) and cellulose tris(4-methylbenzoate) (Chiralcel® OJ-H ). The experimental data were utilized to discuss the effects of the mobile phase composition, the nature of the alcoholic modifier and the specific structural features of the analytes on retention and separation. The elution sequence was determined under the optimized separation conditions. Copyright © 2011 John Wiley & Sons, Ltd. its synthetic intermediates {I ,1 -methyl-3-phenylpiperazine; II ,2 -(4-methyl-2-phenylpiperazino)-3-pyridyl cyanide; III ,2 -(4- methyl-2-phenylpiperazino)nicotinicacid;andIV,(2-(4-methyl-2- phenylpiperazino)-3-pyridyl)methanol} on polysaccharide-based chiral stationary phases (Fig. 1). The separation perfomances were compared, and the effect of the mobile phase composition, the nature of the alcoholic modifier and the specific structural features of the analytes on the retention and separation was discussed. To the best of the authors' knowledge there have been no published reports on the quality control of (S)-MTZ so far in the literature.