Methylprednisolone hemisuccinate

Kong, A.-N. Slaughter, R.L. Jusko, W.J. Simultaneous analysis of methylprednisolone hemisuccinate, cortisol and methylprednisolone by normal-phase high-performance liquid chromatography in human plasma. J.Chromatogr, 1988, 432, 308-314... 

Ebling, W.F. Szefler, S.J. Jusko, W.J. Analysis of cortisol, methylprednisolone, and methylprednisolone hemisuccinate. Absence of effects of troleandomycin on ester hydrolysis. J.Chromatogr., 1984, 305, 271-280... 

A generic enzyme immunoassay for the determination of several synthetic corticosteroids including dexamethasone, betamethasone, flumethasone, triamcinolone, prednisolone, and methylprednisolone in milk, liver, kidney, and muscle samples was recently developed (156). Antibodies raised against dexamethasone-21-hemisuccinate-bovine serum albumin were used in this assay, whereas dexa-methasone-horseradish peroxidase was the label conjugate. Skimmed milk could be directly screened for the presence of corticosteroids at limits of detection of 0.1 ppb for dexamethasone, betamethasone, and flumethasone, 0.3 ppb for triamcinolone and 0.5 ppb for prednisolone. Tissue samples were submitted, prior to the immunoassay, to an extraction/cleanup procedure involving liquid-liquid partitions with acetonitrile-water followed by hexane-chloroform. Background values for bovine liver, swine kidney, and calf muscle were determined to be 0.26, 0.26, and 0.07 ppb, respectively, of dexamethasone equivalents. 

An asthmatic patient using inhaled budesonide and salbutamol developed an acute asthma attack. Despite emergency treatment the patient deteriorated, requiring endotracheal intubation and assisted ventilation, and there was no improvement until the glucocorticoid was withdrawn, after which there was steady improvement. Skin prick tests with prednisolone, sodium hemisuccinate, and 6-methylprednisolone-sodium hemisuccinate were positive. Thirty minutes after intradermal 6-methylprednisolone-sodium hemisuccinate 4 mg, the patient developed a dry cough, dyspnea, and wheezing and a 17% fall in FEVi. 

M. D. Smith, Kinetic study of USP blue tetrazolium assay with methylprednisolone, hydrocortisone, and their hemisuccinate esters by HPLC, J. Pharm. Sci., 69 960 (1980). 

The prodrug approach described above also can be used to alter the solubility characteristics, which, in turn, can increase the flexibility in formulating dosage forms. The solubility of methylprcdnisolonc can be altered from essentially water-insoluble methylpredni.solone acetate to slightly water-insoluble methylprednisolone to water-soluble meth-ylprednisolone. sodium succinate. The water-soluble sodium hemisuccinate salt is used in oral, intravenous, and intramuscular dosage forms. Methylprednisolone itself is normally found in tablels. The acetate ester is found in topical ointments and sterile aqueous suspensions for intramuscular injection. Both the succinate and acetate esters are hydrolyzed to the active methylprednisolone by the patient s own systemic hydrolytic enzymes (esterases). 

Anderson, B. D., Taphouse, V. Initial rate studies of hydrolysis and acyl migration in methylprednisolone 21-hemisuccinate and 17-hemisuccinate. J. PharrrL Sci. 1981, 70,181—186. 

---