Clozapine and norclozapine by LC-MS/MS
Clozapine is an atypical antipsychotic used to treat schizophrenia resistant to conventional therapy. Because of the risk of agranulocytosis, white blood cell counts (WBC) are monitored weekly in the early stages of therapy and monthly thereafter. It is recommended that therapy is withheld if the WBC is less than 3,500 mm-3 and abandoned if the WBC falls below 3000 mm-3 or the granulocyte count below 1,500 mm-3. Side-effects of clozapine include lethargy, hypersalivation, constipation and somnolence. There is a risk of hypotension and seizure at higher doses. A single dose of 300-400 mg may be life-threatening in a clozapine naïve subject. Clozapine is metabolised by N-demethylation, hydroxylation and N-oxidation. The N-demethylated metabolite, norclozapine, is present in plasma at similar concentrations to the parent compound, but has a longer plasma half-life. Plasma clozapine concentrations of 0.35 mg/L and above have been associated with a good response, with the risk of convulsions increasing above 1.0 mg/L.