Human scalp hair as evidence of individual dosage history of haloperidol: a possible linkage of haloperidol excretion into hair with hair pigment

Summary We report a method for determining haloperidol concentration in human scalp hair and discuss a possible linkage of haloperidol excretion into hair with the hair pigment melanin. First, an animal study was conducted to support the idea that hair contains amounts of haloperidol corresponding to the doses given and pigmented hair contains much more drug than does unpigmented hair. The haloperidol concentration was measured using a radioimmunoassay technique after hairs were dissolved in 2.5 N NaOH solution and the drug extracted. Pigmented and albino rats, whose hair from an area on the back had been removed beforehand by plucking, were administered either 1,3, or 10 mg of haloperidol (i.p.) per kg body weight every day for 3 weeks. At the end of the administration period hair which had newly grown on the denuded area was plucked and collected. In each of the two groups classified by hair color the drug levels in the hair correlated with the doses given; however, the concentrations in the hair from the albino rats were much lower than those in the hair from the pigmented rats (which was less than 8.5%). Second, black and white hair was collected from each of seven human subjects with grizzled hair, who were receiving or had been administered haloperidol at fixed daily doses for more than 1 month, and the concentration of haloperidol in each type of hair was measured. In the same subject the concentration in the white hair was found to be much lower than that in the black (less than 10%). In three subjects the dosage had been changed before the hair samplings, and segmental analysis of the distribution of haloperidol in the black hair revealed that the dosage history was imprinted along the length, assuming a hair growth rate of 1 cm/ month; the distribution of drug along the white hair less obviously corresponded to the dosage. Third, another keratinized tissue, nail, was collected together with hair samples from 20 patients and the haloperidol level in the nail was measured and compared with that in the hair. The concentration of haloperidol in nail is only about 3.4% of that in hair. Taken together these results suggest that the mechanism for excreting haloperidol into hair is closely linked with that for the hair pigment melanin.