Characterization of [3H]Flunitrazepam Binding to Melanin

Testorf, Martin F.; Kronstrand, Robert; Svensson, Samuel; Lundström, Ingemar; Ahlner, Johan

doi:10.1006/abio.2001.5364

Cited by 20 publications

(12 citation statements)

References 21 publications

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“…Other studies confirmed these observations in human and animal models for MAMP and N-butylAMP 33 , haloperidol 3435 , codeine 3637 , and cocaine and metabolites 37 . The nature of this interaction is still unclear 38 . Cationic drugs are thought to be ionically bound to the polyanionic melanin molecule 39 .…”

Section: Discussionmentioning

confidence: 99%

Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration

Polettini

Cone²,

Gorelick

et al. 2012

Analytica Chimica Acta

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Background Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Material and Methods Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within one week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng/mg). Results MAMP Tmax occurred from 1 to 2 weeks after both doses, with Cmax ranging from 0.6–3.5 ng/mg after the low and 1.2–5.3 ng/mg after the high MAMP doses. AMP Cmax in hair was 0.1–0.3 ng/mg and 0.2–0.5 ng/mg, respectively, for low and high doses. Highly dose–related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng/mg cutoff for at least two weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15±0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r2=0.90, p=0.00) and AMP (r2=0.94, p=0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between Cmax and melanin. Conclusions This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hair.

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Section: Discussionmentioning

confidence: 99%

Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration

Polettini

Cone²,

Gorelick

et al. 2012

Analytica Chimica Acta

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show abstract

“…Kronstrand et al noted a strong correlation between codeine [21], selegiline [22], and melanin concentrations in human hair; however, the nature of the interaction is still unclear [23]. Cationic drugs are thought to be ionically bound to the polyanionic melanin molecule [24].…”

Section: Incorporation From the Bloodstreammentioning

confidence: 99%

External Contamination

Chatterton

2015

Hair Analysis in Clinical and Forensic Toxicology

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“…ADME: absorption, distribution, metabolism (e.g., phase I and II), excretion/elimination-all affecting half-life and disposition within organism (including depuration); reactivity within organism (e.g., formation of adducts vs. bioconcentration within lipid). Residues that are bound versus those that are free (e.g., particulate-bound APIs may not transport across gills); sequestration and/or bioconcentration of body residues, e.g., within lipids, binding with melanins (Larsson 1993;Testorf et al 2001;Aubry 2002;Roffey et al 2007) and as other adducts; disposition in blood/plasma (primarily bound to proteins), muscle, bile, liver, brain, gonads, eggs, skin, bone, etc. ; these factors also have direct relevance to subsequent human exposure to APls via the food chain (function of edible tissue distribution).…”

Section: Timing Of Exposurementioning

confidence: 99%

“…During development, pigmented melanocytes begin appearing within a day of fertilization. The potential significance of these cells to exposure is related to their high binding affinities for a broad spectrum of xenobiotics, including a wide array of APls known for high affinity to melanin (Testorf et al 2001, Aubry 2002, Roffey et al 2007). Since humans only have melanocyte chromatophores, melanin has been most studied.…”

mentioning

confidence: 99%