Quantitation of a novel metalloporphyrin drug in plasma by atomic absorption spectroscopy.
A bioanalytical method to quantify cobalt mesoporphyrin (CoMP), a novel therapeutic agent, in plasma has been developed and validated. The approach involves atomic absorption spectroscopy to determine total cobalt in a sample and a back-calculation of the amount of compound present. Endogenous plasma cobalt concentrations were small ( <0.2 ng/ml(-1) Co in rat plasma) in comparison to the quantitation limit (4.5 ng/ml(-1) Co). The inter-day imprecision of the method was 10.0% relative standard deviation (RSD) and the inter-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 cannot differentiate between parent drug and metabolites, but negligible metabolism allows reliable estimates of the actual parent drug concentration. A correlation study between the atomic absorption method and 14C-radiometry demonstrated excellent agreement (r = 0.9868, slope = 1.041 +/- 0.028, intercept = 223.7 +/- 190.0) and further substantiated the accuracy of the methods. Methodology was successfully applied to a pharmacokinetic study of CoMP in rat, with pharmacokinetic parameter estimation. The elimination half-lives, after intra-muscular and subcutaneous administration, were 7.7 and 8.8 days, respectively.
Hoffman
K L
KL
Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Feng
M R
MR
Rossi
D T
DT
D000818:Animals; D019540:Area Under Curve; D002250:Carbon Radioisotopes; D003035:Cobalt / Q000097:blood; D005069:Evaluation Studies as Topic; D016014:Linear Models; D008297:Male; D008652:Mesoporphyrins / Q000097:blood*; D011874:Radiometry; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013054:Spectrophotometry, Atomic / Q000379:methods / Q000592:standards
D002250:Carbon Radioisotopes; D008652:Mesoporphyrins; C084061:cobalt mesoporphyrin; D003035:Cobalt