Screening for metabolites of acarviostatin family aminooligosaccharides in rats using ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
An ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC/ESI-MS/MS) procedure was used to identify trace levels of metabolites after the administration of acarviostatin II03 or III03 to rats. Biosamples of the feces and urine of the treated rats as well as the intestinal sacs incubated with the drugs in vitro were pre-treated by cation-exchange extraction, and then applied to a reversed-phase C18 UPLC column with acetonitrile/1.5 mM aqueous ammonia as the mobile solvent. The parent drug and the potential metabolites were identified by two independent qualitative parameters, retention time (tR) and MS/MS spectrum. Seven metabolites were successfully characterized from the intestinal sacs infused with acarviostatin II03 or III03. The metabolic pathways within the intestine were identified including glucose hydrolysis at the reducing terminus, and cyclohexitol hydrolysis at the non-reducing terminus of the parent acarviostatins. Subsequently, we determined that lower amounts of cyclohexitol-lost metabolites compared with the cyclohexitol-containing metabolites, as well as lower amounts of the acarviostatin III03 metabolites compared with the acarviostatin II03 metabolites, could be transferred by the intestinal walls. In the rat feces samples, although the parent compounds could not be found, acarviostatin II03 and III03 both yielded one-glucose-lost and four-glucose-lost types of metabolites. In the rat urine samples, no acarviostatin metabolites could be detected.
Geng
Peng
P
Basic Medical College, Tianjin Medical University, Tianjin 300070, People's Republic of China.
Bai
Gang
G
Meng
Xiansheng
X
Bai
Fang
F
Luo
Guoan
G
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005243:Feces; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D009844:Oligosaccharides / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013302:Streptomyces / Q000378:metabolism; D016482:Urinalysis
D009844:Oligosaccharides