A Previously Unidentified Acepromazine Metabolite in Humans: Implications for the Measurement of Acepromazine in Blood

Elliott, Simon; Hale, Keith A.

doi:10.1093/jat/23.5.367

Cited by 8 publications

(11 citation statements)

References 6 publications

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“…Mechanisms involved in the chemical conversion of compounds that occur both during enzymatic metabolism and degradation due to instability, may include reduction, oxidation, and hydrolysis. [6] The anti-spasmodic drug mebeverine hydrolyzes to form mebeverine alcohol and veratric acid during both in vivo metabolism and chemical degradation. In the analysis of heroin in biological fluids, the parent compound will not be detected as it rapidly metabolizes to 6-monoacetyl morphine (6-MAM) and subsequently morphine, which then undergoes glucuronidation to morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G).…”

Section: Introductionmentioning

confidence: 99%

An investigation of the stability of emerging new psychoactive substances

Soh

Elliott²

2013

Drug Testing and Analysis

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The evolving nature of new psychoactive substances (NPS) - often referred to as 'legal highs', 'designer drugs' or 'bath salts' - presents an evolving challenge for toxicologists. Apart from the detection and identification of these compounds, further analytical challenges may arise from the presence of possible metabolites or degradation products which may have to be considered when devising an analytical strategy. Whilst there has been some stability research for some more established drugs of abuse and medicinal products, data on emerging NPS are less abundant. In order to address this need, 13 NPS (4-MEC, MDAI, methoxetamine, 5-MeO-DALT, 6-APB, MPA, 5-IAI, MDAT, 2-AI, AMT, 25C-NBOMe, AH-7921, 5-MAPB) were spiked in blood and plasma and kept at room temperature (20-23 °C). Detection and identification of the suspected breakdown products were carried out by high performance liquid chromatography with diode-array detection (HPLC-DAD), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultra high performance liquid chromatography with high mass accuracy quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). 4-MEC became undetectable in blood within 14 days with a corresponding loss of 54% in plasma. A breakdown product was identified as dihydro-4-MEC which was also found in vivo in a case work sample. Storage of AMT led to a range of potential breakdown products which were also found in vivo. The remaining substances were found to be stable for at least 21 days in blood and plasma. This is the first time stability data have been published for these emerging substances and showed that additional compounds found during forensic casework were potential metabolites rather than instability products. In particular, presumptive metabolites of 25C-NBOMe and AH-7921 are presented.

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Section: Introductionmentioning

confidence: 99%

An investigation of the stability of emerging new psychoactive substances

Soh

Elliott²

2013

Drug Testing and Analysis

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“…Acepromazine levels (whole blood or plasma) may be sent to a reference laboratory for exposure confirmation. Post-mortem analysis has confirmed the presence of acepromazine in several suicide cases [7,8,14]. Blood levels in these cases ranged from 600-2,400 ng/ml [7,15].…”

Section: Discussionmentioning

confidence: 82%

“…In symptomatic cases of isolated oral acepromazine exposure, the ingested dose ranged from 75-1,250 mg [10,11]. The toxicokinetics of acepromazine in humans has not been described; however, previous analysis has identified 2-(1-hydroxyethyl)promazine as a major metabolite [14]. No whole blood or plasma acepromazine levels have been reported in previous overdose cases (excluding fatalities).…”

Section: Discussionmentioning

confidence: 99%

“…Post-mortem drug levels must be interpreted with caution as in vitro metabolism of the parent compound occurs and may result in erroneously low or absent acepromazine concentrations [14]. Identification of 2-(1-hydroxyethyl)promazine, the major metabolite, may be beneficial in clarifying those cases in which there are negative acepromazine levels [13,14]. Based on its pharmacokinetics, post-mortem drug redistribution likely occurs with acepromazine [7,16].…”

Section: Discussionmentioning

confidence: 99%

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Acute Acepromazine Overdose: Clinical Effects and Toxicokinetic Evaluation

Algren

Ashworth

2014

J. Med. Toxicol.

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“…Elliot and Hale et al [3] reported the possible identification of the major unconjugated metabolite 2(1-hydroxyethyl)-promazine in human urine and blood by high-performance liquid chromatography with diode-array detection (LC-UV). Dewey et al [4] studied the metabolism of acetylpromazine maleate in the horse following an intravenous administration.…”

Section: Introductionmentioning

confidence: 99%

Identification of Acepromazine and Its Metabolites in Horse Plasma and Urine by LC–MS/MS and Accurate Mass Measurement

Wieder¹,

Gray²,

Brown³

et al. 2012

Chromatographia

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Acepromazine maleate (Sedalin Ò ) was administered orally to six thoroughbred horses at a dose of 0.15 mg kg -1 . Urine and blood samples were collected up to 412 h post-administration. Plasma and urine were hydrolysed; plasma samples were then processed using liquid-liquid extraction and urine samples using solid-phase extraction. A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification for acepromazine of 10 pg mL -1 in plasma and 100 pg mL -1 in urine. Acepromazine, hydroxyethylpromazine, hydroxyacepromazine, hydroxyethylpromazine sulphoxide, hydroxyethylhydroxypromazine, dihydroxyacepromazine and dihydroxyhydroxyethylpromazine were detected in the postadministration samples. The parent drug and its metabolites were identified using a combination of UPLC-MS/MS and accurate mass measurement. Separation of the structural isomers hydroxyethylpromazine sulphoxide and hydroxyethylhydroxypromazine was another significant outcome of this work and demonstrated the advantages to be gained from investing in chromatographic method development.

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A Previously Unidentified Acepromazine Metabolite in Humans: Implications for the Measurement of Acepromazine in Blood

Cited by 8 publications

References 6 publications

An investigation of the stability of emerging new psychoactive substances

An investigation of the stability of emerging new psychoactive substances

Acute Acepromazine Overdose: Clinical Effects and Toxicokinetic Evaluation

Identification of Acepromazine and Its Metabolites in Horse Plasma and Urine by LC–MS/MS and Accurate Mass Measurement

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