The liquid chromatographic analysis and pharmacokinetics of the semi-synthetic cephalosporin 3-methyl-7-[4-(1,4,5,6-tetrahydro-2-pyrimidyl)-phenylacetamido]-delta 3-cephalosporanic acid (I).

A high-pressure liquid chromatographic method is described for the analysis of the cephalosporin 3-methyl-7-[4-(1,4,5,6-tetrahydro-2-pyrimidyl)-phenylacetamido]-delta 3-cephalosporanic acid (I) in human plasma and urine. The analysis was carried out on a reverse-phase column and the column effluent was monitored by UV absorption at 236 nm. The lower limits of detection are 0.5 micrograms ml-1 and 0.2 micrograms ml-1 for plasma and urine, respectively. The correlation coefficient for the analysis of this cephalosporin in serum was 0.966 in comparison with a microbiological assay. Plasma and urine levels of (I) in three volunteers given an i.v. dose (500 mg) of the compound have been measured by this method and pharmacokinetic evaluation of the results performed assuming a two-compartment open model. The plasma half-life of the cephalosporin was 0.55 +/- 0.18 h up to 1--2 h after dosing and 2.2 +/- 0.7 h thereafter. At steady-state, the volume of the central compartment was 8--20 l and the volume of distribution was 12--31 l. A comparison of total clearance with renal clearance suggested that 97 +/- 2.6% of the compound would be excreted unchanged via the kidney and this was consistent with that observed experimentally.