Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lamotrigine (LTG) is a novel triazine anticonvulsant currently undergoing clinical trials. LTG N-glucuronide, the major human metabolite of LTG, was isolated from human urine by means of XAD-2 column chromatography and semi-preparative HPLC. The structure of the suspected lamotrigine 2-N-glucuronide was proven by mass spectroscopy and NMR spectroscopy, along with chemical and enzymatic hydrolysis studies. High resolution fast atom bombardment mass spectrometry and Electrospray tandem mass spectrometry of the glucuronide gave an M+ ion at 432.0 amu and a fragment ion at 256.0 (M - 176)+ amu. The proton NMR of the glucuronide indicated the presence of a glucuronic acid moiety. A downfield anomeric proton (5.35-5.60 ppm) implied direct attachment to the aromatic triazine ring. Carbon-13 NMR of the glucuronide revealed an upfield shift (delta = -7.0 ppm) of the C-3 carbon of the triazine ring compared to LTG, indicating attachment of the glucuronide to the N-2 position. Chemical degradation or rearrangement of the glucuronide occurs at neutral pH to produce an unknown product (RP-1), while at basic pH a different unknown product (RP-2) is formed. The glucuronide is unusually stable at acidic pH. Treatment of the glucuronide with beta-glucuronidase resulted in hydrolysis to LTG, and enzymatic hydrolysis was inhibited by saccharo-1,4-lactone.
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PMID:Isolation and characterization of a novel quaternary ammonium-linked glucuronide of lamotrigine. 167 89

The use of thermospray liquid chromatography-mass spectrometry allowed the structural elucidation of a number of urinary metabolites of Lamotrigine, 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine, formed after administering the drug to man, Cynomolgus monkey and rabbit. This data when combined with the data obtained from high-performance liquid chromatography with radiochemical detection enabled us to determine the types and amounts of unchanged drug and metabolites excreted in urine by man and a number of laboratory animal species. This technique was particularly useful as it highlighted a previously unknown fact that Lamotrigine is metabolised to form two different N-glucuronides, one of which is resistant to cleavage in vitro by a crude beta-glucuronidase preparation from Helix pomatia.
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PMID:Use of thermospray liquid chromatography-mass spectrometry to aid in the identification of urinary metabolites of a novel antiepileptic drug, Lamotrigine. 179 36

Lamotrigine, a new antiepileptic drug, is analyzed by capillary zone electrophoresis. Samples were deproteinized with acetonitrile containing an internal standard, acidified with dilute acetic acid and injected into the capillary. The drug migrated rapidly with the cationic compounds in about 3.5 min far from any interfering substances. The test was linear between 0.5-10 mg/l. The analysis time was about 5 min. The CE values correlated well with an HPLC method (r = 0.97; n = 35). The mean serum concentration of 121 patients on this drug was 3.7 mg/l. Incubating the serum with beta-glucuronidase for 1 h increased the peak height of lamotrigine by about 24%.
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PMID:Serum lamotrigine analysis by capillary electrophoresis. 887 47