title: Improving the detection of degradants and impurities in pharmaceutical drug products by applying mass spectral and chromatographic searching.
abstract: Liquid chromatography/mass spectrometry (LC/MS) and NMR are commonly used to identify metabolites, impurities and degradation products in the pharmaceutical industry. To more efficiently deal with the large volumes of data these techniques generate, software programs have been developed by various vendors to assist in the identification of these compounds through the use of spectral and chromatographic search algorithms. The feasibility of using such programs for detecting drug degradants and impurities is assessed. A number of compounds encompassing a wide range of both chemical and pharmaceutical properties were tested using LC/UV/MS and the spectral/chromatographic search algorithm MetaboLynx (Micromass UK Ltd.) to determine the feasibility of detecting analytes at low concentrations. In addition, drug product and stressed drug substance samples containing quinapril hydrochloride, the active ingredient in Accupril tablets, were determined by liquid chromatography with atmospheric pressure ionization-time-of-flight (API LC-TOF) and an API LC-quadrupole (Q) mass spectrometer, and the resulting data was processed using MetaboLynx. The ability of this program to detect and list a variety of analytes known to be present in the samples was evaluated. The combination of LC/UV, LC/MS and spectral/chromatographic searching is a valuable tool for the detection of impurities at low levels.
authors.affiliation: Pharmaceutical Sciences, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
authors.forename: Anita L
authors.initials: AL
authors.lastname: Freed
authors.forename: Uma
authors.initials: U
authors.lastname: Kale
authors.forename: Howard
authors.initials: H
authors.lastname: Ando
authors.forename: David T
authors.initials: DT
authors.lastname: Rossi
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kingsmill
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry / Q000592:standards*
chemical_list: D004364:Pharmaceutical Preparations