Metabolism of cocaine and norcocaine to N-hydroxynorcocaine.

The mixed function oxidase system of mouse liver microsomes converts norcocaine to N-hydroxynorcocaine (NHNC). This metabolite can be measured by high performance liquid chromatography (HPLC) using an electrochemical detector. Experiments with inducers and inhibitors suggested that the cytochrome P-450 system was responsible for most of the formation of NHNC. NHNC was relatively unstable under physiological conditions, with a T 1/2 of 17 min at pH 7.4 and 37 degrees. HPLC with the electrochemical detector was also used to demonstrate the formation of NHNC in vivo when mice were injected with norcocaine or cocaine.