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

Kirby, Brian J.; Hébert, Mary F.; Easterling, Thomas R.; Unadkat, Jashvant D.

doi:10.1016/j.jchromb.2007.10.010

Cited by 18 publications

(18 citation statements)

References 24 publications

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“…Accelerated metabolite elimination could be due to increased secondary oxidative metabolism, increased phase II conjugation, and/or increased renal clearance of the metabolites. In humans, M1 undergoes glucuronidation mediated by uridine 59-diphospho-glucuronosyltransferases (UGTs) and M2b is excreted unchanged in the urine (Naraharisetti et al, 2007). UGT1A1 and UGT1A4 expression is indeed induced during human pregnancy (Feghali and Mattison, 2011); however, mRNA levels of UGTs in pregnant mice are relatively unchanged (Shuster et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Glyburide and metabolite quantification in maternal plasma and fetal homogenates was performed using a previously validated high-performance liquid chromatography-mass spectrometry (HPLC-MS) method with some modifications (Naraharisetti et al, 2007). Most notable was the use of protein precipitation for the isolation of glyburide and metabolites from maternal plasma and fetal homogenates in place of liquid-liquid extraction.…”

Section: Methodsmentioning

confidence: 99%

“…The previously validated HPLC-MS method did not include M2a and M3 for lack of commercially available standards at the time (Naraharisetti et al, 2007). Those standards are now available; therefore, we modified the above method slightly to incorporate the separation and quantification of M1-M3 in maternal plasma.…”

Section: Methodsmentioning

confidence: 99%

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Maternal-Fetal Disposition of Glyburide in Pregnant Mice Is Dependent on Gestational Age

Shuster

Risler

Liang

et al. 2014

J Pharmacol Exp Ther

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Gestational diabetes mellitus is a major complication of human pregnancy. The oral clearance (CL) of glyburide, an oral antidiabetic drug, increases 2-fold in pregnant women during late gestation versus nonpregnant controls. In this study, we examined gestational age-dependent changes in maternal-fetal pharmacokinetics (PK) of glyburide and metabolites in a pregnant mouse model. Nonpregnant and pregnant FVB mice were given glyburide by retro-orbital injection. Maternal plasma was collected over 240 minutes on gestation days (gd) 0, 7.5, 10, 15, and 19; fetuses were collected on gd 15 and 19. Glyburide and metabolites were quantified using high-performance liquid chromatography-mass spectrometry, and PK analyses were performed using a pooled data bootstrap approach. Maternal CL of glyburide increased approximately 2-fold on gd 10, 15, and 19 compared with nonpregnant controls. Intrinsic CL of glyburide in maternal liver microsomes also increased as gestation progressed. Maternal metabolite/glyburide area under the curve ratios were generally unchanged or slightly decreased throughout gestation. Total fetal exposure to glyburide was ,5% of maternal plasma exposure, and was doubled on gd 19 versus gd 15. Fetal metabolite concentrations were below the limit of assay detection. This is the first evidence of gestational age-dependent changes in glyburide PK. Increased maternal glyburide clearance during gestation is attributable to increased hepatic metabolism. Metabolite elimination may also increase during pregnancy. In the mouse model, fetal exposure to glyburide is gestational age-dependent and low compared with maternal plasma exposure. These results indicate that maternal glyburide therapeutic strategies may require adjustments in a gestational age-dependent manner if these same changes occur in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Maternal-Fetal Disposition of Glyburide in Pregnant Mice Is Dependent on Gestational Age

Shuster

Risler

Liang

et al. 2014

J Pharmacol Exp Ther

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“…7 In recent years, a highly sensitive assay for the determination of glyburide at sub-ng/mL concentrations using liquid chromatography-mass spectrometry has been developed and validated. 8 In 2009, Hebert et al published a study evaluating the pharmacokinetics of glyburide in women with GDM. The limit of detection for glyburide was 0.25 ng/mL.…”

Section: Level Of Evidence: IIImentioning

confidence: 99%

Glyburide Transport Across the Human Placenta

Schwartz

Rosenn

Aleksa³

et al. 2015

Obstetrics &Amp; Gynecology

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“…The maternal plasma and fetal GLB concentrations were determined by a validated HPLC/MS assay (Naraharisetti et al, 2007). In brief, a stock solution of GLB was prepared in pure acetonitrile at 0.25 mg/ml, and it was diluted to 2.5 or 25 g/ml in methanol/water (1:1, v/v).…”

Section: H(n)]glyburide ([ 3 H]glb) (40-70mentioning

confidence: 99%

The Breast Cancer Resistance Protein (Bcrp1/Abcg2) Limits Fetal Distribution of Glyburide in the Pregnant Mouse: An Obstetric-Fetal Pharmacology Research Unit Network and University of Washington Specialized Center of Research Study

Zhou¹,

Wang²,

Unadkat³

et al. 2007

Mol Pharmacol

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Breast cancer resistance protein (BCRP) is most abundantly expressed in the apical membrane of placental syncytiotrophoblasts, suggesting that it may protect the fetus by impeding drug penetration across the placental barrier. Glyburide (GLB) is an antidiabetic drug routinely used to treat gestational diabetes. In this study, we first determined whether GLB is a BCRP/Bcrp1 substrate. The intracellular [3 H]GLB concentrations in Madin-Darby canine kidney (MDCK)/BCRP cells were significantly lower than those in MDCK/vector cells. The addition of 10 M fumitremorgin C, a specific BCRP inhibitor, significantly increased the intracellular [ 3 H]GLB concentrations approximately 2-fold in MDCK/BCRP cells, but it had no effect in MDCK/vector cells. Similar results were obtained using MDCKII parent and MDCKII/Bcrp1 cells. GLB was also shown to be a BCRP/Bcrp1 substrate in transwell transport experiments. We then examined whether Bcrp1 limits fetal distribution of GLB in the pregnant mouse. GLB was administered by retro-orbital injection to the wild-type and Bcrp1 Ϫ/Ϫ pregnant mice. The maternal plasma samples and fetuses were collected at various times (0.5-240 min) after drug administration. The GLB concentrations in the maternal plasma samples and homogenates of fetal tissues were determined by high-performance liquid chromatography/mass spectrometry. Although the maternal plasma area under the concentration-time curves (AUCs) of GLB in the wild-type and Bcrp1 Ϫ/Ϫ pregnant mice were comparable, the fetal AUC of GLB in the Bcrp1 Ϫ/Ϫ pregnant mice was approximately 2 times greater than that in the wild-type pregnant mice. These results suggest that GLB is a BCRP/Bcrp1 substrate, and Bcrp1 significantly limits fetal distribution of GLB in the pregnant mouse, but it has only a minor effect on the systemic clearance of the drug.

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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

Cited by 18 publications

References 24 publications

Maternal-Fetal Disposition of Glyburide in Pregnant Mice Is Dependent on Gestational Age

Maternal-Fetal Disposition of Glyburide in Pregnant Mice Is Dependent on Gestational Age

Glyburide Transport Across the Human Placenta

The Breast Cancer Resistance Protein (Bcrp1/Abcg2) Limits Fetal Distribution of Glyburide in the Pregnant Mouse: An Obstetric-Fetal Pharmacology Research Unit Network and University of Washington Specialized Center of Research Study

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