Analysis of lamotrigine and lamotrigine 2-N-glucuronide in guinea pig blood and urine by reserved-phase ion-pairing liquid chromatography

J Chromatogr. 1991 Nov 15;571(1-2):217-30. doi: 10.1016/0378-4347(91)80448-l.

Abstract

Lamotrigine is an investigational anticonsulvant drug undergoing clinical trials. A simultaneous assay was developed to quantitate lamotrigine and its major metabolite, lamotrigine 2-N-glucuronide, from guinea pig whole blood. The extraction procedure and reversed-phase high-performance liquid chromatographic (HPLC) assay employed sodium dodecylsulfate (SDS) as an ion-pairing reagent to selectively separate lamotrigine and lamotrigine 2-N-glucuronide from endogenous blood components, other anti-convulsant drugs, and their metabolites. The mobile phase was composed of acetonitrile-50 mM phosphoric acid (pH 2.2) containing 10 mM SDS (33:67, v/v), and components were detected at 277 nm. The total coefficients of variance (C.V.) for the blood assay were less than or equal to 9.4% for lamotrigine (0.25-20.0 micrograms/ml) and less than or equal to 13.4% for the glucuronide metabolite (0.25-10.0 micrograms/ml). Separate assays for lamotrigine and its glucuronide in urine were developed. In order to quantitate low levels of lamotrigine in guinea pig urine, lamotrigine was extracted with tert.-butyl methyl ether-ethyl acetate (1:1). The total C.V. for lamotrigine quantitation in urine was less than or equal to 7.5% (0.10-10.0 micrograms/ml). For the determination of lamotrigine 2-N-glucuronide, urine was diluted with an SDS-phosphoric acid buffer (1:4) and injected directly onto the HPLC system, total C.V. less than or equal to 4.2% (0.5-50 micrograms/ml).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / blood*
  • Anticonvulsants / urine*
  • Chromatography, High Pressure Liquid / methods*
  • Guinea Pigs
  • Lamotrigine
  • Male
  • Triazines / blood*
  • Triazines / urine*

Substances

  • Anticonvulsants
  • Triazines
  • lamotrigine 2-N-glucuronide
  • Lamotrigine