Incorporation of Drugs for the Treatment of Substance Abuse into Pigmented and Nonpigmented Hair

Wilkins, Diana G.; Valdez, Angelique S.; Nagasawa, Pamela R.; Gygi, Steven P.; Rollins, Douglas E.

doi:10.1021/js970360t

Cited by 25 publications

(12 citation statements)

References 53 publications

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“…This finding is consistent with the results reported by Goodwin et al [2] and Wilkins et al [5]. At the same time, it is a remarkable finding in view of the fact that a higher concentration of the parent drug compared to that of its dealkylated metabolite is mostly detectable in hair, such as e.g.…”

Section: Discussionsupporting

confidence: 92%

“…Also, a reasonable positive relationship could be reached between the hair assay result and the daily dose referred to the individual's body weight if the sum of BUP and NBUP concentrations was considered. An approximate dose-dependent increase of BUP/NBUP concentrations in pigmented hair could be established in a rat model [5]. BUP being a cation at physiologic pH (pK a = 8.5, 10.0), the drug is expected to be incorporated into pigmented hair to a greater extent than into non-pigmented hair.…”

Section: Discussionmentioning

confidence: 99%

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Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

et al. 2011

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It is still a matter of debate whether a positive correlation between the dose and the amount of drug in the hair exists. Drugs such as buprenorphine (BUP) used under controlled conditions present an opportunity to prove a possible relationship. Due to discrepant findings of BUP/norbuprenorphine (NBUP) ratios in hair, in vitro degradation of both analytes in diluted acid was also investigated. The levels of BUP and NBUP in proximal hair sections from 18 subjects participating in a maintenance program were determined by liquid chromatography/tandem mass spectrometry following incubation with methanol and subsequent liquid/liquid extraction. BUP and NBUP were incubated in diluted hydrochloric acid at 60°C for up to 24 h. The alleged rearrangement products were simultaneously monitored. All hair samples tested positive for BUP (lower limit of detection-0.238 ng/mg hair) and NBUP (0.043-0.961 ng/mg hair). The concentration of NBUP in hair was consistently higher than that of BUP except for a single specimen. Degradation of BUP and NBUP was dependent on time; hydrolysis of NBUP occurred faster than that of BUP. The concentration of BUP and NBUP will be underestimated if analytes are recovered by acidic procedures. NBUP should be monitored in hair samples besides BUP for the sum of both BUP and NBUP may provide an estimate of BUP exposure following long-term administration of the drug.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

et al. 2011

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“…37 Infant hair is continually exposed to drug in amniotic fluid, and specimens were not washed prior to analysis. Consistent with previous publications, 10, 38–39 EMDP was not found in infant hair, and only occasionally in maternal hair.…”

Section: Discussionsupporting

confidence: 92%

Methadone and Metabolites in Hair of Methadone-Assisted Pregnant Women and Their Infants

Himes

Goodwin

Rock

et al. 2012

Therapeutic Drug Monitoring

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Methadone is the recommended pharmacotherapy for opioid-dependent pregnant women. The primary aims of this study were to determine whether a dose-concentration relationship exists between cumulative maternal methadone dose, methadone and metabolite concentrations in maternal hair during pregnancy and whether maternal hair methadone and metabolite concentrations predict neonatal outcomes. Materials and Methods Hair specimens were collected monthly from opioid-dependent mothers enrolled in methadone treatment and 4 of their infants. Hair specimens were segmented (3cm), washed (maternal hair only) and analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP) by liquid chromatography tandem mass spectrometry. Results There was large inter-subject variability and no dose-concentration relationship for cumulative methadone dose and methadone, EDDP, EMDP or total concentrations in hair. For individual women, a positive trend was noted for cumulative methadone dose and methadone and EDDP concentrations in hair. There was a positive linear trend for cumulative methadone dose and EDDP/methadone ratio in maternal hair, perhaps reflecting methadone’s induction of its own metabolism. Maternal methadone concentrations were higher than those in infant hair, and infant EDDP hair concentrations were higher than those in maternal hair. Maternal methadone dose, and methadone and EDDP hair concentrations were not correlated with peak infant neonatal abstinence syndrome (NAS) scores, days to peak NAS, duration of NAS, time to NAS onset, birth length, head circumference or amount of neonatal morphine pharmacotherapy. Maternal cumulative 3rd trimester methadone dose was positively correlated with infant birth weight. Conclusion Methadone and EDDP in pregnant women’s hair are markers of methadone exposure and do not predict total methadone dose, nor neonatal outcomes from in utero methadone exposure.

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“…In a preliminary study HaCaT and Sk-Mel-1 cell lines have been already used to study differential drug uptake by pigment-and non-pigment-producing cells mimicking chronic drug consumption in forensic hair analysis [17]. The results obtained for 3 H-haloperidol were in accordance with previous observations for substances with high melanin affinity from animal studies [3,5,6,14,18,25,26] and in vitro binding experiments [1,15,16] which demonstrated that pigments act as scavengers and accumulate those substances.…”

Section: Introductionsupporting

confidence: 81%

Preliminary approach to elucidate the role of pigment as a binding site for drugs and chemicals in anagen hairs: pigments as carriers for 3 H-haloperidol in HaCaT/Sk-Mel-1 co-cultures

Pötsch

Emmerich

Skopp

2002

International Journal of Legal Medicine

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In view of the melanin-binding characteristics of haloperidol and its differential uptake by pigment- and non-pigment-producing cells, a co-culture of HaCaT with Sk-Mel-1 cell lines was performed to investigate whether melanosomes act as carriers for drug molecules associated with the pigments. Initially, HaCaT and Sk-Mel-1 cells were separately cultivated in the presence of 3H-haloperidol (400 pmol/ml medium ) for 28 days followed by subsequent co-cultivation in the absence of 3H-haloperidol for 5 days. The transfer of pigments into the keratinocytes during co-culture was confirmed by transmission electron microscopy. After the co-culture experiments a striking increase (> or = 50%) of 3H-haloperidol was observed in the pigmented HaCaT cells compared to the unpigmented keratinocytes. The present study proved the role of pigments as carriers for melanin-associated drug molecules. The results supported the hypothesis that hair pigment might be a factor affecting the outcome of hair assays for particular categories of commonly used licit and illicit substances. The chosen cell lines and the developed co-culture system may represent suitable in vitro models to study differential drug uptake into cell populations present in the skin or in the growing hair follicle as well as to elucidate drug uptake due to melanocyte-keratinocyte interactions.

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Incorporation of Drugs for the Treatment of Substance Abuse into Pigmented and Nonpigmented Hair

Cited by 25 publications

References 53 publications

Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

Methadone and Metabolites in Hair of Methadone-Assisted Pregnant Women and Their Infants

Preliminary approach to elucidate the role of pigment as a binding site for drugs and chemicals in anagen hairs: pigments as carriers for 3 H-haloperidol in HaCaT/Sk-Mel-1 co-cultures

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