DETERMINATION OF THE ARPROMIDINE-TYPE HISTAMINE H-2-RECEPTOR AGONIST )PROPYL]-N-2-[3-(1H-IMIDAZOL-4-YL)PROPYL]GUANIDINE AND CORRESPONDING N-3-ALKOXYCARBONYLGUANIDINES BY HPLC AND CE1

The highly potent cardiohistaminergic )propyl]-N-2-[3-(1H-imidazol-4-y l)propyl]guanidine 1 and the corresponding putative prodrugs, the N-et hoxycarbonyl and N-Boc-substituted guanidines 2 and 3, were analysed b y isocratic reversed phase ion-pairing HPLC and capillary zone electro phoresis (CZE) using W-detection. At 210 nm the limits of detection of the high precision HPLC method (Nucleosil 100-7, C-18, 52% methanol/4 8% sodium, phosphate buffer (50 mM, pH 3.0) containing 25 mM sodium pe ntanesulphonate, 1 ml/min, 65 degrees C) were around 0.1 mu M with a s ample size of 50 mu l and between 2-4 mu M for the optimised CZE metho d (fused silica capillary (75 cmX50 mu m I.D.), 200 mM lithium phospha te buffer, pH 6.0 hydrodynamic injection (20 psi . s) 20 kV; 30 degree s C) with a reproducible sample size of approx. 34 nl. The HPLC method was applied to determine the binding of 1 to serum albumin and to ana lyse 1-3 in serum, with dansyl-L-phenylalanine as internal standard, w here as hydrolysis kinetics of 2 and 3 were measured with CZE. In addi tion, compounds 1-3 were quantified in urine by CZE using quinine sulp hate as internal standard.