HAIR ANALYSIS FOR DRUGS OF ABUSE .10. EFFECT OF PHYSICOCHEMICAL PROPERTIES OF DRUGS ON THE INCORPORATION RATES INTO HAIR

To determine the mechanism involved, the incorporation rate (ICR) of d rugs into hair was compared to melanin affinity, lipophilicity and mem brane permeability. The following 20 drugs were tested; amphetamine, m ethamphetamine, p-hydroxyamphetamine, p-hydroxymethamphetamine, cocain e, benzoylecgonine, ecgonine methyl ester, morphine, 6-acetylmorphine, phencyclidine, 1-(1-phenyl)-piperidinyl-cyclohexanol, methylenedioxya mphetamine, methylenedioxymethamphetamine, methoxyphenamine, O-desmeth yl methoxyphenamine, benzphetamine, norbenzphetamine, deprenyl, lyserg ic acid diethylamide (LSD) and 11-nortetrahydrocannabinol-9-carboxylic acid (THCA). Their ICRs were represented as the ratios of the drug co ncentrations in rat hair to AUCs (the areas under the concentration vs . time curves) in rat plasma. Cocaine had the highest incorporation ra te understood and there was a 3600 fold difference between the ICR of cocaine and that of THCA, the lowest drug. The melanin affinity of the se drugs was determined by incubating a test solution with melanin at 36 degrees C in the dark for 2 h. After incubation and centrifugation, the drug concentration in the filtrate was determined by GC/MS or LC. The drug most affinitive to melanin was cocaine, followed by benzphet amine, phencyclidine, methylenedioxymethamphetamine and LSD. The corre lation coefficient between ICR and melanin affinity of the 20 drugs wa s 0.947 (0.949 excluding THCA). Lipophilicity was calculated from the retention times of HPLC according to Kaliszan's method. Although the c orrelation coefficient between ICR and lipophilicity was very low (0.2 01), it rose to 0.770 by removing only THCA. The combination of melani n affinity and lipophilicity brought about a higher correlation (0.979 ) with the ICRs. Our data also suggested that the higher ICRs of basic drugs than neutral or acidic ones are strongly related to the membran e permeability of the drug based on the pH gradient between blood (pH 7.4) and hair matrix (acidic).