Reference

Strategies in the design of solution-stable, water-soluble prodrugs

Strategies in the design of solution-stable, water-soluble prodrugs. II: Properties of micellar prodrugs of methylprednisolone. Anderson, B. D.; Conradi, R. A.; Knuth, K. E.; Nail, S. L. (Coll. Pharm., Univ. Utah, Salt Lake City, UT 84112, USA). J. Pharm. Sci., 74(4), 375-81 (English) 1985. CODEN: JPMSAE. ISSN: 0022-3549. DOCUMENT TYPE: Journal CA Section: 63 (Pharmaceuticals) Section cross-reference(s): 22, 32 The advantages of micellar prodrugs as water-sol. delivery systems for parenteral administration of relatively insol. parent drugs are studied. The micelles, in addn. to their water-soly., solubilize poorly sol. degrdn. products which may otherwise ppt. and may act as a self-stabilizing influence due to protection of the hydrolytically labile prodrug linkage within the micelle interior. Two 21-esters I [91573-56-7] and II [90350-40-6] of methylprednisolone [83-43-2] previously identified as having promising dil. soln. stability, showed self-assocn. in aq. soln. at higher concns., detd. by soly., kinetic, and light-scattering measurements. Free methylprednisolone, the product of prodrug hydrolysis, is solubilized in concd. prodrug formulations. Acid- and base-catalyzed hydrolysis rate consts. are altered in the micelles, resulting in further prolongation of shelf life in concd. solns.

High-performance liquid chromatographic determination of methylprednisolone and methylprednisolone 21-[8-[methyl-(2-sulfoethyl)amino]-8-oxoctanoate] sodium salt in human plasma

High-performance liquid chromatographic determination of methylprednisolone and methylprednisolone 21-[8-[methyl-(2-sulfoethyl)amino]-8-oxoctanoate] sodium salt in human plasma. Shah, Jyoti A.; Weber, Dennis J.; Bothwell, Brian E. (Drug Metab. Res., Upjohn Co., Kalamazoo, MI 49001, USA). J. Chromatogr., 414(1), 1-10 (English) 1987. CODEN: JOCRAM. ISSN: 0021-9673. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) An HPLC assay method with UV detection at 243 nm was developed for the quant. detn. of methylprednisolone (MP) [83-43-2] and methylprednisolone 21-[8-[methyl-(2-sulfoethyl)amino]-8-oxoctanoate] sodium salt (MPSO) [90350-40-6] in human plasma. The method was simple, rapid, and sensitive to detect MP and MPSO in human plasma following administration of therapeutic doses of MPSO. The assay procedure involved stabilization of plasma samples by addn.There are some reagents with their cas registry numbers 83-43-2 and 90350-40-6 are used in this study. of Na2 EDTA and ion-pair extns. of MPSO with (Et)4NCl. After extg. both the drugs and internal std. into chloroform, the ext. was evapd. to dryness under N. The resulting residue was reconstituted in 200-500 mL of mobile phase and chromatographed on a C18 IBM reversed-phase column (5 mm). The mobile phase was a mixt. of water-acetonitrile-isopropanol (.9:10) contg. 50 mL of 0.1M HCl and 0.497 g (Et)4NCl. Propyl-p-hydroxybenzoate was used as an internal std. The chromatog. responses were linear at f200 mg/mL for MP and 80 mg/mL for MPSO in human plasma. The assay detection limit was ~7 ng/mL for MP and 25 ng/mL for MPSO in human plasma. Statistical anal. indicated an av. recovery of 102.0% for MP and 75.2% for MPSO. Human plasma levels were reported for MP and MPSO following single-dose i.v. administration of 100 mg equiv of MPSO. .