title: Structural elucidation of stress degradation products of ampicillin sodium by liquid chromatography/hybrid triple quadrupole linear ion trap mass spectrometry and liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry.
abstract: BACKGROUND
  Clinical adverse reactions to ampicillin sodium are closely related to its impurities and degradation products. Several unknown degradation products have been detected in the degradation samples of ampicillin sodium. Therefore, a sensitive and accurate method is required to rapidly identify unknown degradation products.
  
  
  METHODS
  Ampicillin sodium was subjected to forced degradation under hydrolytic (acidic and alkaline), hot, photolytic, and humid stress conditions. A combination of liquid chromatography/hybrid triple quadrupole linear ion trap mass spectrometry (LC/QqLIT-MS) and liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (LC/QqTOF-MS) was used to identify unknown degradation products. The analysis was achieved with gradient elution on an Agilent Zorbax SB-C18 column using ammonium acetate (1 mmol/L, pH 3.5) and acetonitrile.
  
  
  RESULTS
  A total of 19 degradation products and impurities, including five novel degradation products, were identified and characterized in the forced conditions. The novel degradation products were separately identified as (Z)-2-amino-N-((2-oxo-3-phenyl-2,3,6,7-tetrahydro-1H-1,4-diazepin-5-yl)methylene)-2-phenylacetamide (m/z 349), 2-(1-(2-amino-2-phenylacetamido)-2-((carboxy(phenyl)methyl)amino)-2-oxoethyl-5,5-dimethyl-4,5-dihydrothiazole-4-carboxylic acid (m/z 499), (E)-2-(((3,6-dioxo-5-phenyl-1,6-dihydropyrazin-2(3H)-ylidene)methyl)amino)-3-mercapto-3-methylbutanoic acid (m/z 348), 5-(amino(phenyl)methyl)-7-formyl-2,2-dimethyl-2,3-dihydroimidazo[5,1-b]thiazole-3-carboxylic acid (m/z 332), and 2-(1-(2-amino-2-phenylacetamido)-2-((2-(((4-carboxy-5,5-dimethylthiazolidin-2-yl)methyl)amino)-2-oxo-1-phenylethyl)amino)-2-oxoethyl)-5,5-dimethylthiazolidine-4-carboxylic acid (m/z 673).
  
  
  CONCLUSIONS
  LC/QqTOF-MS allowed us to obtain more accurate, richer information than LC/QqLIT-MS for the qualitative analysis of unknown compounds. Forced degradation studies could provide us with the data needed to understand the degradation pathways and intrinsic stability of drugs, and to simultaneously validate the feasibility of the analytical procedure.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Xuanlin
authors.initials: X
authors.lastname: Xu
authors.forename: Shan
authors.initials: S
authors.lastname: Fu
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Kerong
authors.initials: K
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhao
authors.forename: Weijing
authors.initials: W
authors.lastname: Ding
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000667:Ampicillin / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D004355:Drug Stability; D013058:Mass Spectrometry / Q000379:methods*
chemical_list: D000667:Ampicillin