title: Pharmaceutical application of LC-MS. 1--Characterization of a famotidine degradate in a package screening study by LC-APCI MS.
abstract: The application of LC-MS to characterize low-level degradates in pharmaceutical dosage formulations is a new and challenging field. In a package screening study, a low-level degradate of famotidine (1, 3-[[[2-[[aminoiminomethyl]-amino]-4-thiazolyl]methyl] thio]-N-(aminosulphonyl)-propanimid-amide, an H2-receptor antagonist, molecular weight: 337) was detected by HPLC in film-coated tablets packaged in child-resistant (CR) foil pouches which were stressed at 40 degrees C/75% relative humidities (RH) for 4 months. LC-atmospheric pressure chemical ionization (APCI) mass spectrometry using positive ion mode yielded a molecular weight of 349 for the degradate, suggesting that it was formed by the addition of one carbon to the famotidine molecule. A detailed analysis of the positive product ion mass spectrum of the protonated degradate ion in a LC-MS-MS study indicated that the carbon was added to the side of N-(aminosulphonyl)-propanimid-amide of famotidine. The structure of the degradate was determined to be 2, which was confirmed by LC-APCI MS and HPLC study of the product formed from the reaction of famotidine with formaldehyde--a one-carbon reagent.
authors.affiliation: Merck Research Laboratories, West Point, PA 19486.
authors.forename: X Z
authors.initials: XZ
authors.lastname: Qin
authors.forename: D P
authors.initials: DP
authors.lastname: Ip
authors.forename: K H
authors.initials: KH
authors.lastname: Chang
authors.forename: P M
authors.initials: PM
authors.lastname: Dradransky
authors.forename: M A
authors.initials: MA
authors.lastname: Brooks
authors.forename: T
authors.initials: T
authors.lastname: Sakuma
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D015738:Famotidine / Q000032:analysis* / Q000737:chemistry; D005557:Formaldehyde / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure
chemical_list: D005557:Formaldehyde; D015738:Famotidine