Metabolic profile of glyburide in human liver microsomes using LC-DAD-Q-TRAP-MS/MS.
The sulfonylurea urea drug glyburide (glibenclamide) is widely used for the treatment of diabetes milletus and gestational diabetes. In previous studies monohydroxylated metabolites were identified and characterized for glyburide in different species, but the metabolite owing to the loss of cyclohexyl ring was identified only in mouse. Glyburide upon incubation with hepatic microsomes resulted in 10 metabolites for human. The current study identifies new metabolites of glyburide along with the hydroxylated metabolites that were reported earlier. The newly identified drug metabolites are dihydroxylated metabolites, a metabolite owing to the loss of cyclohexyl ring and one owing to hydroxylation with dehydrogenation. Among the 10 identified metabolites, there were six monohydroxylated metabolites, one dihydroxylated metabolite, two metabolites owing to hydroxylation and dehydrogenation, and one metabolite owing to the loss of cyclohexyl ring. New metabolites of glyburide were identified and characterized using liquid chromatography-diode array detector-quadruple-ion trap-mass spectrometry/mass spectrometry (LC-DAD-Q-TRAP-MS/MS). An enhanced mass scan-enhanced product ion scan with information-dependent acquisition mode in a Q-TRAP-MS/MS system was used to characterize the metabolites. Liquid chromatography with diode array detection was used as a complimentary technique to confirm and identify the metabolites. Metabolites formed in higher amounts were detected in both diode array detection and mass spectrometry detection.
Department of Biotransformation, Drug Metabolism and Pharmacokinetics Unit, Sai Life Sciences Limited, International Biotech Park, Phase-II, Hinjewadi, Pune-411 057, India. selvan_ravindran@yahoo.com
Selvan
S
Ravindran
Sudipta
S
Basu
Santosh Kapil Kumar
SK
Gorti
Prashant
P
Surve
Navya
N
Sloka
D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005905:Glyburide / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D006865:Hydrogenation; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008970:Molecular Weight; D053719:Tandem Mass Spectrometry / Q000379:methods*
D005905:Glyburide