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A reversed-phase high-performance liquid chromatographic assay using electrochemical detection in the reductive mode has been developed for the analysis of 4-bromo-2,7-dimethoxy-3H-phenothiazin-3-one (1) in plasma to determine drug absorption. Free drug in plasma in concentrations as little as 0.25ng/mL can be estimated with a mean coefficient of variation (CV) of 6.3 ± 2.6%. Metabolites which can be converted to the parent drug by acid hydrolysis can be quantified in concentrations of 10ng/mL or more, with a mean CV of 4.3 · 1.9%. To test the procedure, plasma was obtained from dogs receiving 14Clabeled 1.After acid hydrolysis of plasma, the electrochemical assay for parent drug showed good agreement with the radioactive equivalents in plasma, suggesting that parent drug and metabolites can be satisfactorily analyzed by this procedure.

A reversed-phase high-performance liquid chromatographic method using coulometric electrochemical detection in the oxidative mode has been developed for the analysis of 3-(9-chloro-5, 6-dihydro-11-H-pyrrolo[2,1-b][3]benzazepine-11-ylidene-N, N-dirnethyl-1-propanamine E)-Z-butenedioate hydrogen maleate (1) in plasma of patients dosed with 2–8 mg/kg/d of the drug. Concentrations as little as 0.1 ng/mL of 1 in plasma can be estimated with a mean coefficient of variation of 7.4 ± 1.08%. The utility of the procedure was demonstrated by the analysis of 500 patient samples from a rising multiple-dose study.

1. A modification of the methyl orange technique for basic amines has been developed for the determination of Dromoran in plasma, urine and gastro-intestinal tract contents.