Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration

Goodwin, Robert S.; Wilkins, Diana G.; Averin, Olga; Choo, Robin E.; Schroeder, Jennifer R.; Jasinski, Donald R.; Johnson, Rolley E.; Jones, Hendrée E.; Huestis, Marilyn A.

doi:10.1373/clinchem.2007.091413

Cited by 25 publications

(27 citation statements)

References 14 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%

“…A first study showing a statistically significant association between the cumulative dose of BUP and its concentration in hair from nine subjects has been published by Goodwin et al [2]. BUP is metabolized mainly by N-dealkylation via CYP3A4 to norbuprenorphine (NBUP) and then by glucuronidation [3].…”

Section: Introductionmentioning

confidence: 99%

“…BUP is metabolized mainly by N-dealkylation via CYP3A4 to norbuprenorphine (NBUP) and then by glucuronidation [3]. Both the parent drug and its N-dealkyl metabolite have been detected in hair; however, there was a discrepancy with regard to BUP/NBUP concentration ratios between studies [2]. Some authors reported higher NBUP concentrations in hair, whereas in some studies BUP was detected in higher concentrations than NBUP.…”

Section: Introductionmentioning

confidence: 99%

“…Some authors reported higher NBUP concentrations in hair, whereas in some studies BUP was detected in higher concentrations than NBUP. Though the acidic extraction was not considered to account for the discrepant results [2], this aspect has not been followed up.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

et al. 2011

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“…Enfin, les cheveux ont également été testés [29], avec un seuil de positivité fixé à 10 pg/mg sur une prise d'essai de 30 mg de cheveux, permettant d'obtenir 8 % de faux positifs et là encore l'absence de faux négatif. Contrairement à la méthadone, les concentrations les plus importantes retrouvées dans les cheveux sont celles du métabolite et non celles mesurées pour le produit parent [35,36].…”

Section: Les Recherches En Immunoanalyseunclassified

Le dépistage immunochimique des médicaments substitutifs de l'héroïne et autres opioïdes

Alvarez

2009

Ann Toxicol Anal

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Résumé -Selon l'Observatoire Français des Drogues et Toxicomanie, en 2007, de 12 000 à 15 000 patients étaient traités par méthadone et plus de 80 000 par buprénorphine. Pouvoir effectuer un dépistage rapide de ces deux molécules par immunoanalyse est donc important, aussi bien pour vérifier la compliance, obligatoire pour les patients traités par méthadone, que dans un cadre médico-légal où ces molécules sont retrouvées dans plus de 8 % des recherches de causes de décès. De nombreuses études ont été publiées à ce jour sur les différents tests commercialisés. Ceux-ci sont le plus souvent validés pour un usage dans les urines, mais également dans le sang total, le plasma, le sérum, la salive et/ou les cheveux en ce qui concerne les kits ELISA. Les seuils de positivité varient de 5 à 300 ng/mL pour la méthadone et de 0,5 à 5 ng/mL pour la buprénorphine en fonction des tests et des matrices biologiques. Dans les cheveux, les seuils proposés sont de l'ordre de 200 pg/mg pour la méthadone et de 10 pg/mg pour la buprénorphine. L'EDDP, principal métabolite de la méthadone, ne croise pas avec l'anticorps dirigé contre la méthadone, mais il existe des tests spécifiques pour l'EDDP. Pour la buprénorphine, les taux de croisement avec la norbuprénorphine varient de 1 à 100 %. Différentes molécules fréquemment prescrites comme le vérapamil, certains neuroleptiques, la diphénydramine et la doxylamine peuvent parfois donner des résultats faussement positifs avec les tests méthadone et le tramadol ou la dihydrocodéine avec ceux pour la buprenorphine. Plus récemment, des tests d'immunoanalyse permettant la recherche des nouveaux opioïdes utilisés en thérapeutique et ne croisant pas ou partiellement avec la recherche classique des opiacés ont été développés. C'est le cas notamment du dextropropoxyphène, de l'oxycodone et du fentanyl. Ces tests, sur lesquels relativement peu d'études sont encore disponibles, peuvent s'avérer intéressants dans certains cas. Mots clés : Immunoanalyse, méthadone, buprénorphine, traitements de substitution, opioïdesAbstract -In France in 2007, between 12 000 and 15 000 patients were treated by methadone and more than 80 000 by buprenorphine. A rapid detection of these two compounds has to be available for the monitoring of these patients, or in forensic cases since these compounds are found in more than 8% of the deceases. Many studies were published on the different marketed tests. All these tests were validated in urine, but many of them, notably ELISA tests, were also validated in whole blood, serum, plasma, oral fluid or hair. The used cut-offs were in the range 5-300 ng/mL for methadone and 0.5-5 ng/mL for buprenorphine depending on the tests and the matrix. In hair, the proposed cut-offs were 200 pg/mg for methadone and 10 pg/mg for buprenorphine. The cross-reactivity of EDDP, the main metabolite of methadone, is very low, but some tests used a specific antibody for this metabolite. The cross-reactivity of norbuprenorphine, the main metabolite of buprenorphine, is in the range 1-100%. False-posi...

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Buprenorphine and nor‐buprenorphine levels in head hair samples from former heroin users under Suboxone® treatment

Belivanis

Tzatzarakis

Vakonaki

et al. 2014

Drug Testing and Analysis

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In the current study, buprenorphine (BUP) and its major metabolite, nor-buprenorphine (NBUP), were determined in hair samples from former heroin users following Suboxone® treatment. Hair samples from 36 subjects were analyzed. The drugs of interest were isolated from hair by solid-liquid extraction with methanol and were determined by liquid chromatography-mass spectrometry, using an electrospray ionization interface. The analytical parameters of the method (such as linearity, limits of quantification, recovery, accuracy, and precision) were determined. The inter-quartile range of BUP levels was from 11.4 to 37.4 pg/mg (mean value 56.6 pg/mg) for the proximal hair segment, from 5.8 to 43.3 pg/mg for the middle hair segment (mean value 25.3 pg/mg), while a range from 4.3 to 33.9 pg/mg (mean value 105.2 pg/mg) for the distant to the root hair segment was determined. For NBUP the corresponding inter-quartile range was from 27.0 to 147.6 for the proximal segment (mean value 95.4 pg/mg), from 21.5 to 164.7 pg/mg for the middle segment (mean value 102.0 pg/mg) and from 20.4 to 103.6 pg/mg for the distant segment (mean value 156.8 pg/mg). The mean BUP/NBUP concentration ratio was 0.5. The daily dose of Suboxone® correlated significantly with BUP and NBUP levels in hair (p = 0.001 and p = 0.023) as well as with the BUP/NBUP ratio (p = 0.010). No significant correlation was found between the levels of BUP and NBUP and the duration of Suboxone® administration. The developed and validated method was successfully used for the determination of BUP and NBUP in hair samples collected from former heroin users under Suboxone® treatment.

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Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration

Cited by 25 publications

References 14 publications

Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage

Le dépistage immunochimique des médicaments substitutifs de l'héroïne et autres opioïdes

Buprenorphine and nor‐buprenorphine levels in head hair samples from former heroin users under Suboxone® treatment

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