Chromatographic methods development, validation and degradation characterization of the antithyroid drug Carbimazole.

The current paper reports the development and validation of stability-indicating HPLC and HPTLC methods for the separation and quantification of main impurity and degradation product of Carbimazole. The structures of the degradation products formed under stress degradation conditions, including hydrolytic and oxidative, photolytic and thermal conditions, were characterized and confirmed by MS and IR analyses. Based on the characterization data, the obtained degradation product from hydrolytic conditions was found to be methimazole-impurity A of Carbimazole as reported by the British Pharmacopeia and the European Pharmacopeia. A stability-indicating HPLC method was carried out using a Zorbax Eclipse Plus CN column (150 × 4.6 mm i.d, 5 µm particle size) and a mobile phase composed of acetonitrile-0.05 m KH2 PO4 (20: 80, v/v) in isocratic elution, at a flow rate of 1 mL/min. The method was proved to be sensitive for the determination down to 0.5% of Carbimazole impurity A. Additionally, a stability-indicating chromatographic HPTLC method was achieved using cyclohexane-ethanol (9:1, v/v) as a developing system on HPTLC plates F254 with UV detection at 225 nm. The proposed HPLC and HPTLC methods were successfully applied to Carbimazole® tablets with mean percentage recoveries of 100.12 and 99.73%, respectively.

Study of the British Pharmacopeia method on methimazole (thiamazole) content in carbimazole tablets.

The analysis of carbimazole tablets in The British Pharmacopoeia, 1993, includes a quantitative thin layer chromatography (TLC) determination of methimazole. Repeated analysis of the same samples did not give similar results. The repeatability and reproducibility of the method was studied. It was proved that the residence time of the methimazole spot on the TLC plate is time dependent.

Reactions of 1-methyl-2-mercaptoimidazole with hypochlorous acid and superoxide.

Reactions of thioureylene antithyroid drugs (1-methyl-2-mercaptoimidazole and carbimazole) with hypochlorous acid (HOCl) and superoxide were followed optically and products were analyzed by mass spectrometry. 1-methyl-2-mercaptoimidazole (MMI) and carbimazole reacted rapidly with HOCl with a rate constant of 1 x 10(7) and 7 x 10(6) M(-1)s(-1), respectively. The characteristic spectrum assigned to MMI disulfide appeared immediately after addition of HOCl, followed by a slow conversion to a final spectrum. The conversion was dependent upon the ratio of HOCl to MMI and both antithyroid drugs uptake 3 moles HOCl for complete conversion. A similar sequence of spectral changes was also observed when the HOCl was replaced by myeloperoxidase (MPO)/H2O2/Cl- system. The final oxidation product of MMI and carbimazole with HOCl and superoxide was 1-methylimidazole.

Antithyroid drug carbimazole and its analogues: synthesis and inhibition of peroxidase-catalyzed iodination of L-tyrosine.

Synthesis and biological activity of the antithyroid drug carbimazole (CBZ) and its analogues are described. The introduction of an ethoxycarbonyl group in methimazole and its selenium analogue not only prevents the oxidation to the corresponding disulfide and diselenide but also reduces the zwitterionic character. A structure-activity correlation in a series of CBZ analogues suggests that the presence of a methyl substituent in CBZ and related compounds is important for their antithyroid activity.