DETERMINATION OF N-G-NITRO-L-ARGININE AND N-G-NITRO-L-ARGININE METHYL-ESTER IN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

An HPLC method has been developed for the measurement of the nitric ox ide synthase inhibitors, N-G-nitro-L-arginine (L-NOLA) and N-G-nitro-L -arginine methyl ester (L-NAME), in sheep plasma. Using an ion-exchang e HPLC column (JWAS 150, 100 x 3.9 mm I.D., Millipore-Waters, Australi a) and post-column ninhydrin detection, L-NOLA was separated from vali ne and other plasma amino acids. When added to sheep plasma, good reco very (mean 102%) and precision (mean coefficient of variation 2.7%) in the measurement of L-NOLA was obtained over the range 2-50 mg/l. L-NA ME was unstable in sheep plasma at 37 degrees C, and was converted to L-NOLA with a half-life of 250 min. This method will permit pharmacoki netic parameters to be determined for these potential drugs, and will allow plasma drug concentrations to be correlated with the pharmacodyn amic effects of these compounds.