Abstract
1. Three conjugated metabolites of haloperidol were isolated from urine of patients on haloperidol and purified by h.p.l.c. with immunological detection, using three types of anti-haloperidol antisera.
2. Structures of the metabolites were: a sulphate conjugate of the 2-hydroxylated 4-fluorophenyl ring of reduced haloperidol (MH-1), a glucuronide conjugate at the same position as MH-1 (MH-2), and a glucuronide conjugate of the hydroxy group of haloperidol (MH-3).
3. MH-3 was the main urinary metabolite in volunteers receiving haloperidol, who excreted 18% of the dose in the 24h urine as MH-3, while other conjugates were less than 1%. MH-3 could not be hydrolysed with β-glucuronidase, due to steric hindrance.
4. Immunological detection of conjugated metabolites is very useful in metabolic studies in humans because of its sensitivity and specificity.