Therapeutic monitoring of chlorpromazine. III: Minimal interconversion between chlorpromazine and metabolites in human blood.

Chlorpromazine (CPZ), chlorpromazine sulfoxide (CPZSO), and chlorpromazine N-oxide (CPZNO) were each incubated (37 degrees C), for various timed intervals up to 60 min, with pooled human whole blood. Plasma and red blood cells were then separated and analyzed by a high performance liquid chromatographic method that avoids the use of alkaline extraction procedures. It was found that CPZ, CPZSO, and CPZNO were remarkably stable in whole blood under physiological conditions. CPZ was converted into CPZSO to a small extent (1%). Reports of 15-50% conversion of CPZ into CPZSO are largely due to artifacts, which result when red blood cell materials come into contact with alkali. CPZNO was recovered (85%) unchanged from the plasma. A small portion (1%) of the CPZNO was reduced to CPZ in the red blood cells. Thus, on the basis of these in vitro data, blood does not appear to be an important tissue for the metabolism of CPZ, CPZSO, or CPZNO.