title: Evaluation, synthesis and characterization of tacrolimus impurities.
abstract: Tacrolimus is an immunosuppressant macrolactam of fermentative origin. By means of HPLC, LC-MS and NMR analyses, coupled with the reference standard synthesis, the main impurities of tacrolimus bulk drug samples were identified and their chemical-physical properties reported. Known ascomycin and tautomers I and II were detected. The correct relative retention time HPLC value of 39,40-dihydro tacrolimus was established. The not described 23,24-anhydro derivative was detected and completely characterized. A full characterization of ascomycin and 39,40-dihydro tacrolimus was also reported.
authors.affiliation: Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università degli Studi di Milano, Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferraboschi
authors.forename: Diego
authors.initials: D
authors.lastname: Colombo
authors.forename: Maria
authors.initials: M
authors.lastname: De Mieri
authors.forename: Paride
authors.initials: P
authors.lastname: Grisenti
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004340:Drug Contamination; D007166:Immunosuppressive Agents / Q000032:analysis* / Q000592:standards; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D012015:Reference Standards; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification / Q000592:standards
chemical_list: D007166:Immunosuppressive Agents; C058028:immunomycin; D016559:Tacrolimus