Clozapine and Norclozapine

Clozapine and norclozapine by LC-MS/MS
Clinical details: 
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.
Reference range: 

0.35-0.50 mg/L.

Sample type and Volume required: 
2 mL of EDTA whole blood preferred (pre-dose or ‘trough’ sample). Serum or plasma can be used if required, but please avoid gel-separator tubes.
Turnaround time: 
2 working days
Storage and transport: 
Please refrigerate (if possible) if not sending immediately. Send by first class post.
Toxicology Department at King's Hospital
020 3299 5881
King's College Hospital
Bessemer Wing - 3rd Floor
Denmark Hill
London SE5 9RS
For clinical advice or interpretation of results, please contact the laboratory in the first instance.

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Last updated: 18/07/2017