Use of thermospray liquid chromatography-mass spectrometry to aid in the identification of urinary metabolites of a novel antiepileptic drug, Lamotrigine.
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.
Doig
M V
MV
Department of Bioanalytical Sciences, Wellcome Research Laboratories, Beckenham, Kent, UK.
Clare
R A
RA
D000818:Animals; D000927:Anticonvulsants / Q000652:urine*; D002250:Carbon Radioisotopes; D002853:Chromatography, Liquid / Q000379:methods*; D005965:Glucuronates / Q000652:urine; D006801:Humans; D000077213:Lamotrigine; D008252:Macaca fascicularis; D013058:Mass Spectrometry / Q000379:methods*; D011817:Rabbits; D014227:Triazines / Q000652:urine*
D000927:Anticonvulsants; D002250:Carbon Radioisotopes; D005965:Glucuronates; D014227:Triazines; D000077213:Lamotrigine