Desalkylflurazepam found in patients’ samples after high‐dose midazolam treatment

Vogt, Susanne; Kempf, Jürgen; Buttler, Jürgen; Auwärter, Volker; Weinmann, Wolfgang

doi:10.1002/dta.1484

Cited by 7 publications

(4 citation statements)

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“…(Table S5). 19 Furthermore, the presence of 3-hydroxynorflurazepam and the absence of norflurazepam in biological samples could be due to an uptake of cinolazepam (own unpublished data, Moosmann et al). This is because norflurazepam is the active metabolite of other benzodiazepines such as flurazepam and fludiazepam and can also be detected in some cases of midazolam administration, as it is used as a precursor in the synthesis of midazolam and can be present up to one percent in the medicine.…”

Section: Norflurazepam (Norfludiazepam N-desalkyflurazepam)mentioning

confidence: 99%

“…This is because norflurazepam is the active metabolite of other benzodiazepines such as flurazepam and fludiazepam and can also be detected in some cases of midazolam administration, as it is used as a precursor in the synthesis of midazolam and can be present up to one percent in the medicine. 19 Furthermore, the presence of 3-hydroxynorflurazepam and the absence of norflurazepam in biological samples could be due to an uptake of cinolazepam (own unpublished data, Moosmann et al).…”

Section: Norflurazepam (Norfludiazepam N-desalkyflurazepam)mentioning

confidence: 99%

“…18 Additionally, norflurazepam has been detected after high-dose midazolam treatment in serum samples of patients. 19 Based on the pharmacological activity of compounds like diazepam and nordazepam (nor-diazepam), 20 demethylation can be expected to lead to a lower pharmacological potency of norflurazepam compared to fludiazepam. This is supported by a study of Waters et al who utilized a quantitative structure-activity (QSAR) approach to predict the binding affinities of 22 designer benzodiazepines.…”

Section: Introductionmentioning

confidence: 99%

“…2016, three new benzodiazepines were offered as research chemicals via the Internet. Additionally, norflurazepam has been detected after high-dose midazolam treatment in serum samples of patients 19. Availability of this metabolite as a research chemical could complicate the interpretation of analytical findings or might lead to incorrect conclusions since norflurazepam is one of the main target analytes for detecting flurazepam intake 18.…”

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confidence: 99%

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Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines: An update comprising flunitrazolam, norflurazepam, and 4'‐chlorodiazepam (Ro5–4864)

Moosmann

Bisel

Westphal³

et al. 2019

Drug Testing and Analysis

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The number of newly appearing benzodiazepine derivatives on the new psychoactive substances (NPS) drug market has increased over the last couple of years totaling 23 'designer benzodiazepines' monitored at the end of 2017 by the European Monitoring Centre for Drugs and Drug Addiction. In the present study, three benzodiazepines [flunitrazolam, norflurazepam, and 4′-chlorodiazepam (Ro5-4864)] offered as 'research chemicals' on the Internet were characterized and their main in vitro phase I metabolites tentatively identified after incubation with pooled human liver microsomes. For all compounds, the structural formula declared by the vendor was confirmed by gas chromatography−mass spectrometry (GC-MS), liquid chromatography−tandem mass spectrometry (LC MS/MS), liquid chromatography−quadrupole time of flight−mass spectrometry (LC−QTOF−MS) analysis and nuclear magnetic resonance (NMR) spectroscopy. The metabolic steps of flunitrazolam were monohydroxylation, dihydroxylation, and reduction of the nitro function. The detected in vitro phase I metabolites of norflurazepam were hydroxynorflurazepam and dihydroxynorflurazepam. 4'-Chlorodiazepam biotransformation consisted of N-dealkylation and hydroxylation. It has to be noted that 4′-chlorodiazepam and its metabolites show almost identical LC-MS/MS fragmentation patterns to diclazepam and its metabolites (delorazepam, lormetazepam, and lorazepam), making a sufficient chromatographic separation inevitable. Sale of norflurazepam, the metabolite of the prescribed benzodiazepines flurazepam and fludiazepam, presents the risk of incorrect interpretation of analytical findings.

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Section: Norflurazepam (Norfludiazepam N-desalkyflurazepam)mentioning

confidence: 99%

Section: Norflurazepam (Norfludiazepam N-desalkyflurazepam)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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