Hair Analysis for Drugs of Abuse. X. Effect of Physicochemical Properties of Drugs on the Incorporation Rates into Hair.

Abstract

To determine the mechanism involved, the incorporation rate (ICR) of drugs into hair was compared to melanin affinity, lipophilicity and membrane permeability. The following 20 drugs were tested; amphetamine, methamphetamine, p-hydroxyamphetamine, p-hydroxymethamphetamine, cocaine, benzoylecgonine, ecgonine methyl ester, morphine, 6-acetylmorphine, phencyclidine, 1-(1-phenyl)-piperidinyl-cyclohexanol, methylenedioxyamphetamine, methylenedioxymethamphetamine, methoxyphenamine, O-desmethyl methoxyphenamine, benzphetamine, norbenzphetamine, deprenyl, lysergic acid diethylamide (LSD) and 11-nortetrahydrocannabinol-9-carboxylic acid (THCA). Their ICRs were represented as the ratios of the drug concentrations in rat hair to AUCs (the areas under the concentration vs. time curves) in rat plasma. Cocaine had the highest incorporation rate understood and there was a 3600 fold difference between the ICR of cocaine and that of THCA, the lowest drug. The melanin affinity of these 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 benzphetamine, phencyclidine, methylenedioxymethamphetamine and LSD. The correlation coefficient between ICR and melanin affinity of the 20 drugs was 0.947 (0.949 excluding THCA). Lipophilicity was calculated from the retention times of HPLC according to Kaliszan's method. Although the correlation coefficient between ICR and lipophilicity was very low (0.201), it rose to 0.770 by removing only THCA. The combination of melanin 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 membrane permeability of the drug based on the pH gradient between blood (pH 7.4) and hair matrix (acidic).

Exposures associated with clandestine methamphetamine drug laboratories in Australia

“…In relation to the quantification methamphetamine and amphetamine in hair samples, there are a wide range of methods (192,193,196,206,(209)(210)(211)(212)(213)(214)(215)(216) that rely on the sampling of different quantities of hair (that have the potential to affect the laboratory quantitation limit), potential inclusion of segment analysis (for evaluation of exposure over time), utilisation of different extraction methods and inclusion of methods for the evaluation of deposited and/ or absorbed contamination. The washing of hair during analysis needs to be undertaken with caution as some methods have the potential to damage the hair shaft and affect the reporting of absorbed methamphetamine and amphetamine (194).…”

Hair Analysis for Pharmaceutical Drugs. I. Effective Extraction and Determination of Phenobarbital, Phenytoin and Their Major Metabolites in Rat and Human Hair.

“…According to our previous studies, 14) the ICRs of methamphetamine and cocaine were 0.29 and 3.58, while benzoylecgonine and tetrahydrocannabinolic acid show low ICRs (0.003 and 0.0005). The ICRs of PB and PPH were determined to be 0.0014 and 0.0016, respectively.…”

“…Drug Incorporation Rate into Hair We have designed 14) a model experiment with DA rats for comparing the incorporation rates into hair (ICRs) of many kinds of drugs. Drugs were administered to DA rats once a day, usually at 5 mg/kg intraperitoneally for 10 successive days.…”

“…Our group has proposed 14,17) an ICR based on the ratios of hair concentrations and plasma AUC as an index of bloodhair pharmacokinetics. These theories are, however, only general guidelines for prediction, as other factors influence incorporation and binding in hair.…”

Gas Chromatography-High-Resolution Mass Spectrometric Method for Determination of Methamphetamine and its Major Metabolite Amphetamine in Human Hair

“…There have been several reports of studies for their determination in human hair. Analytical methods have used high-performance liquid chromatography (HPLC) (8)(9)(10)(11)(12), gas chromatography (GC) (13), gas chromatography-mass spectrometry (GC-MS) (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), capillary electrophoresis (25,26), and liquid chromatography-mass spectrometry (22,(27)(28)(29). Because of its specificity and sensitivity, gas chromatography-low-resolution mass spectrometric (GC-LRMS) method with the selected ion monitoring technique was routinely employed for the determination of methamphetamine abuse.…”