title: Validation of a sensitive LC-MS assay for quantification of glyburide and its metabolite 4-transhydroxy glyburide in plasma and urine: an OPRU Network study.
abstract: Glyburide (glibenclamide, INN), a second generation sulfonylurea is widely used in the treatment of gestational diabetes mellitus (GDM). None of the previously reported analytical methods provide adequate sensitivity for the expected sub-nanogram/mL maternal and umbilical cord plasma concentrations of glyburide during pregnancy. We developed and validated a sensitive and low sample volume liquid chromatographic-mass spectrometric (LC-MS) method for simultaneous determination of glyburide (GLY) and its metabolite, 4-transhydroxy glyburide (M1) in human plasma (0.5 mL) or urine (0.1 mL). The limits of quantitation (LOQ) for GLY and M1 in plasma were 0.25 and 0.40 ng/mL, respectively whereas it was 1.06 ng/mL for M1 in urine. As measured by quality control samples, precision (% coefficient of variation) of the assay was <15% whereas the accuracy (% deviation from expected) ranged from -10.1 to 14.3%. We found that the GLY metabolite, M1 is excreted in the urine as the glucuronide-conjugate.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Box 357610, University of Washington, Seattle, WA 98195-7610, United States.
authors.forename: Suresh Babu
authors.initials: SB
authors.lastname: Naraharisetti
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Kirby
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Easterling
authors.forename: Jashvant D
authors.initials: JD
authors.lastname: Unadkat
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016640:Diabetes, Gestational / Q000097:blood / Q000652:urine; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D005905:Glyburide / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011247:Pregnancy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C526862:4-transhydroxy glyburide; D005966:Glucuronidase; D005905:Glyburide