title: Identification of sanguinarine metabolites in pig liver preparations by accurate mass measurements using electrospray ionization hybrid ion trap/time-of-flight mass spectrometry.
abstract: BACKGROUND
  Sanguinarine (SA) is currently used in veterinary medicine for animal husbandry as a natural component of feed additive Sangrovit. To date, SA metabolism in food-producing animals has not yet been reported. Therefore, the purpose of the present study was to investigate the metabolism of SA in pig liver microsomes and cytosol.
  
  
  METHODS
  The SA incubations mixtures of microsomes and cytosol were processed by trichloroacetic acid (TCA) and acetonitrile. Then, the samples were analyzed using a sensitive and reliable method based on liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry (LC-IT/TOFMS). The structural elucidations of these metabolites were performed by comparing the changes in the accurate molecular masses and product ions generated from precursor ions with those of the parent drug.
  
  
  RESULTS
  Seven metabolites were identified in pig liver preparations. Dihydrosanguinarine (DHSA, m/z 334) was the main metabolite formed in liver microsomes and the only one in cytosol. One oxidative metabolite and two O-demethylenated metabolites of SA (m/z 320) were found in the TCA-treated microsomal samples. However, SA pseudobase and two additional O-demethylenated metabolites of DHSA (m/z 322) were found only in the acetonitrile-treated microsomal samples.
  
  
  CONCLUSIONS
  It was demonstrated that different metabolites of SA were identified depending on the acidic or neural extraction conditions. A metabolic pathway of SA in pig was tentatively proposed based on these characterized metabolites and early reports.
authors.affiliation: College of Forestry, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Hua-Hai
authors.initials: HH
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhi-Liang
authors.initials: ZL
authors.lastname: Sun
authors.forename: Zhao-Ying
authors.initials: ZY
authors.lastname: Liu
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D053119:Benzophenanthridines / Q000737:chemistry / Q000378:metabolism*; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D034421:Sus scrofa / Q000378:metabolism*; D019155:Veterinary Drugs / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; D019155:Veterinary Drugs; C005705:sanguinarine