Micellar electrokinetic and high-performance liquid chromatographic determination of potential manufacturing impurities in pholcodine

Quantitative high-performance liquid chromatographic (HPLC) and micellar el ectrokinetic chromatographic (MEKC) methods have been developed for the det ermination of four structurally related potential manufacturing impurities, including morphine, of the opiate derivative pholcodine. Pholcodine and th e four impurities were separated by MEKC in less than 14 min using a 70 cmX 75 mum I.D. uncoated fused-silica capillary (25 kV at 30 degreesC) and a ru nning buffer consisting of 10% acetonitrile (v/v) in 20 mM borate-phosphate buffer pH 8.0 containing 40 mM sodium dodecyl sulphate (SDS). The MEKC met hod was compared to a HPLC method using a 5 mum Luna phenyl-hexyl column (1 50x4.6 mm I.D.) eluted with a mobile phase consisting of a mixture of 10% ( v/v) acetonitrile, 7% (v/v) tetrahydrofuran in 20 mM phosphate buffer pH 8. 0. Both methods were fully validated and a comparison was made regarding se lectivity, linearity, precision, robustness and limits of detection and qua ntitation. The presence of the impurities in different samples of pholcodin e drug substance was investigated using both methods. (C) 2000 Elsevier Sci ence B.V. All rights reserved.