Quantitation of a novel metalloporphyrin drug in plasma by atomic absorption spectroscopy

A bioanalytical method to quantify cobalt mesoporphyrin (CoMP), a novel the rapeutic agent, in plasma has been developed and validated. The approach in volves atomic absorption spectroscopy to determine total cobalt in a sample and a back-calculation of the amount of compound present. Endogenous plasm a cobalt concentrations were small (< 0.2 ng ml(-1) Co in rat plasma) in co mparison to the quantitation limit (4.5 ng ml(-1) Co). The inter-day imprec ision of the method was 10.0% relative standard deviation (RSD) and the int er-day bias was +/- 8.0% relative error (RE) over a standard curve range of 4.5-45.0 ng ml(-1) Co. Because it quantifies total cobalt, the method cann ot differentiate between parent drug and metabolites, but negligible metabo lism allows reliable estimates of the actual parent drug concentration. A c orrelation study between the atomic absorption method and C-14-radiometry d emonstrated excellent agreement (I = 0.9868, slope = 1.041 +/- 0.028, inter cept = 223.7 +/- 190.0) and further substantiated the accuracy of the metho ds. Methodology was successfully applied to a pharmacokinetic study of CoMP in rat, with pharmacokinetic parameter estimation. The elimination half-li ves, after intra-muscular and subcutaneous administration, were 7.7 and 8.8 days, respectively. (C) 1999 Elsevier Science B.V. All rights reserved.