Quantitative determination of 21-hydroxy-deflazacort in human plasma using gradient semi-microbore liquid chromatography.
A sensitive and selective liquid chromatographic procedure to quantitate the deflazacort metabolite 21-hydroxy-deflazacort (DF-21OH) in human plasma was developed and validated. DF-21OH and fludrocortisone acetate (internal standard, IS) were isolated from human plasma (2 mL) by solid-phase extraction onto C-18 cartridges. Potential interferences were selectively removed and analytes were eluted with ethyl acetate. Following evaporation, the residue was reconstituted for HPLC analysis. Separation was achieved by gradient elution using a 5 microns YMC Basic column (2.0 x 100 mm) with mobile phases consisting of 20% methanol and 50% acetonitrile in 50 mM phosphate buffer (pH 3) at a temperature of 50 degrees C. Flow rate was maintained at 0.3 mL/min., and analytes were quantified spectrophotometrically at 246 nm. The assay was validated over the range 1.0 to 500 ng/mL DF-21OH. Calibration curves were prepared using a weighted (1/concentration) nonlinear quadratic regression algorithm. Peak-height ratios were proportional to the amount of DF-21OH added to plasma. Assay precision (%RSD) ranged from 4.2 to 11%, with a corresponding assay accuracy (% relative error) of +/- 2.8%. Absolute recovery of DF-21OH from plasma was 78-86% over the concentration range. The minimum quantitation limit was 1.0 ng/mL.
Simultaneous determination of the two main metabolites of deflazacort in human plasma by high-performance liquid chromatography.
Deflazacort t , Flantadin ®, is a synthetic oxazolino steroid with a high glucocorticoid activity, which at present is in the launch phase as a systemic anti-inflammatory agent [1, 2]. The anti-inflammatory potency of deflazacort in comparison with prednisolone has been found to be 0.82 in rheumatoid arthritis and other diseases [3]. In clinical trials deflazacort has been observed to influence calcium balance and carbohydrate metabolism to lesser degrees than prednisolone [4, 5]. The metabolism of deflazacort in the rat, dog, monkey and man follows a common route consisting of rapid de-acetylation to deflazacort-21-alcohol (M II), and of 6-13hydroxylation of this to form 6-13-hydroxy-deflazacort-21-alcohol (M III) (Fig. 1). The
Unusual (Z)-selective palladium(II)-catalysed addition of aryl boronic acids to vinylaziridines.
The palladium(II)-catalysed addition of arylboronic acids to vinylaziridines has been developed. This reaction proceeds via an insertion/ring-opening process to provide (Z)-allylsulfonamides preferentially. This stereoselectivity is complimentary to existing methods that typically proceed via a SN2' mechanism to yield (E)-allylsulfonamides. Electron-deficient arylboronic acids were the optimum substrates for this reaction, while electron-donating groups on the aromatic ring of the boronic acids resulted in moderate yields.