title: Urinary profile of methylprednisolone acetate metabolites in patients following intra-articular and intramuscular administration.
abstract: A study on urinary metabolites of methylprednisolone acetate (MPA) has been performed by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) in precursor ion scanning (PIS) and neutral loss (NL) modes. Patients suffering from joint inflammation have been treated with Depo-Medrol® (MPA marketed suspension, 40 mg) intra-articularly (IA) and after a wash-out period, intramuscularly (IM) at the same dose. Urine samples have been collected after both the administration routes. Metabolites were identified in PIS mode by setting the fragment ion at m/z 161 which is specific for MPA, methylprednisolone (MP), methylprednisolone hemisuccinate, and in NL mode by selecting the losses of 54, 72, 176 and 194 Da. The MP-related structure of each target ion detected in both the MS modes was then confirmed by MS/MS acquisitions, and by accurate mass experiments. By using this approach, 13 MPA metabolites (M1-M13) have been identified, nine already reported in the literature and four unknown and for which the chemical structures have been proposed. No differences in the metabolic pattern of MPA when administered IM or IA were observed. The relative abundances of metabolites compared with the internal standard (MP-D2) were monitored by multiple reaction monitoring analysis for 19 days after both the administration routes.
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. alessia.panusa@iss.it
authors.forename: Alessia
authors.initials: A
authors.lastname: Panusa
authors.forename: Luca
authors.initials: L
authors.lastname: Regazzoni
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Aldini
authors.forename: Marica
authors.initials: M
authors.lastname: Orioli
authors.forename: Arrigo
authors.initials: A
authors.lastname: Giombini
authors.forename: Paola
authors.initials: P
authors.lastname: Minghetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Tranquilli
authors.forename: Marina
authors.initials: M
authors.lastname: Carini
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007270:Injections, Intra-Articular; D007273:Injections, Intramuscular; D008775:Methylprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000652:urine; D000077555:Methylprednisolone Acetate; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
chemical_list: D000077555:Methylprednisolone Acetate; D008775:Methylprednisolone