Synthesis, high-performance liquid chromatography-nuclear magnetic resonance characterization and pharmacokinetics in mice of CD271 glucuronide

Retinoic acid-glucuronides are known as retinoids with activity in acne the rapy, Limited placental transfer acid reduced retinoid adverse effects. We synthesized the glucuronide of a novel retinoid, CD271 (adapalene), used fo r the treatment of moderate acne. The synthesis product ("CD271 glucuronide ", CD271G) was purified by preparative HPLC. It undergoes in aqueous soluti on, like other glucuronides, rapid acyl-migration of the bound aglycone lea ding to position isomers. Thus characterization of purified CD271G could be only achieved by HPLC-NMR coupling. A subfraction ("CD271GB") consisting e ssentially of 2'- and 3'-CD271G was used for pharmacokinetic studies. After a single subcutaneous injection at a dosage of 30 mg/kg the substance show ed considerable uptake and metabolism to CD271 indicating that CD271GB coul d serve as a prodrug for CD271. (C) 2001 Elsevier Science B.V. All rights r eserved.