Use of antisera in the isolation of human specific conjugates of haloperidol

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 24 h urine as MH-3, while other conjugates were less than 1%. MH-3 could not be hydrolysed with beta-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.