Chiral analysis of methylphenidate and dextromoramide by capillary electrophoresis.

Capillary electrophoretic methods have been developed to separate the enantiomers of methylphenidate (MPH) and dextromoramide. For MPH separation was achieved with heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMCD) as chiral selector in a 100 mM phosphoric acid buffer adjusted to pH 3.0 with triethanolamine. Commercial samples of D,L-erytho-MPH HCl and D,L-threo-MPH HCl were analysed using the method. There was no evidence of the presence of D,L-threo-MPH HCl in D,L-erytho-MPH HCl and vice versa. The ratio of the enantiomers was determined for each diastereoisomer. Hydroxypropyl-beta-cyclodextrin was the chiral selector of choice for the chiral separation of the enantiomers of moramide. The separation which gave a resolution of about 3.5 was achieved in 4 min using only a 6 cm of length of capillary. In a sample of dextro-R-moramide tartrate only a small quantity (4.9% w/w) of levo-S-moramide was detected with this method.

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

Quantitative high-performance liquid chromatographic (HPLC) and micellar electrokinetic chromatographic (MEKC) methods have been developed for the determination of four structurally related potential manufacturing impurities, including morphine, of the opiate derivative pholcodine. Pholcodine and the four impurities were separated by MEKC in less than 14 min using a 70 cm x 75 microm I.D. uncoated fused-silica capillary (25 kV at 30 degrees C) and a running 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 method was compared to a HPLC method using a 5 microm Luna phenyl-hexyl column (150 x 4.6 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 selectivity, linearity, precision, robustness and limits of detection and quantitation. The presence of the impurities in different samples of pholcodine drug substance was investigated using both methods.

Isolation and identification of three potential impurities of pholcodine bulk drug substance.

Three previously unreported manufacturing impurities were isolated from a pholcodine mother liquor using preparative reversed-phase HPLC. The liquor was the residue remaining after recrystallisation of a production batch of pholcodine. The impurities, which are structurally related to pholcodine, were initially detected by thin-layer chromatography (TLC). Their structures were determined after separation by preparative HPLC (Econo-Prep 5 microm C18 column, 30 cm x 21.2 mm i.d.). Structure elucidation was carried out using nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and ultra violet (UV) spectroscopy. The impurities were identified as alkylated derivatives of pholcodine possessing second 2-morpholinoethyl substituents at various positions.