Determination of drugs of abuse and pharmaceuticals in skeletal tissue by UHPLC–MS/MS

Orfanidis, Amvrosios; Gika, Helen; Mastrogianni, Orthodoxia; Krokos, Adamantios; Theodoridis, Georgios; Zaggelidou, Eleni; Raikos, Νikolaos

doi:10.1016/j.forsciint.2018.07.004

Cited by 43 publications

(31 citation statements)

References 17 publications

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“…Citalopram, clomipramine, and their respective metabolites are detectable in all sampled bone types. Observed skeletal tissue concentrations are comparable with those obtained from similar studies previously published and exceed those seen in blood . Citalopram is found in substantially higher concentration than clomipramine.…”

Section: Discussionsupporting

confidence: 88%

“…Observed skeletal tissue concentrations are comparable with those obtained from similar studies previously published and exceed those seen in blood. 10,26,27 Citalopram is found in substantially higher concentration than clomipramine. When drug concentrations of the different bone types are compared to each other within a rat, a big variability (>36%) is seen trend is seen; however the results are not as significant.…”

Section: Discussionmentioning

confidence: 99%

“…In the past, many different extraction procedures have been described for components in bone tissue. In our study, a simple extraction procedure was applied on full bones using methanol . Drug levels in different bones from various anatomical body sites of chronic‐dosed rats were compared and the accumulation of drugs and their metabolites were assessed in these sites.…”

Section: Introductionmentioning

confidence: 99%

“…Over the last few years, many studies have been published dealing with extraction methodologies and detection of drugs in skeletal tissue which mostly apply mass spectrometry (MS) or tandem MS (MS/MS techniques coupled to either gas chromatography (GC) or liquid chromatography (LC). [9][10][11] Despite the growing knowledge about this matrix, interpretation of the found concentrations remains very difficult. To have a basis for interpreting analytical results from skeletal tissue, all different factors that influence bone drug concentrations need to be investigated.…”

Section: Introductionmentioning

confidence: 99%

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Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats

Vandenbosch

Somers

Cuypers

2019

Drug Testing and Analysis

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In recent years, the use of skeletal tissue as an alternative matrix in forensic toxicology has received new interest. In cases where extreme decomposition has taken place, analysis of skeletal tissue is often the only option left. In this article, a fully validated method is presented and the distribution of clomipramine, citalopram, midazolam, and metabolites after chronically administration is examined within skeletal tissue. Rats were chronically dosed with respectively clomipramine, citalopram, or midazolam. Extracts were quantitatively analyzed using liquid chromatography−electrospray ionization−tandem mass spectrometry (LC−ESI−MS/MS). Clomipramine, citalopram, and metabolites, respectively desmethylclomipramine and desmethylcitalopram are shown to be detectable in all bone types sampled. Midazolam and its metabolite α‐OH‐midazolam could not be detected. The absence of midazolam in extracts gives an indication that drugs with pKa values under physiological pH are badly or not incorporated in bone tissue. Bone and post‐mortem blood concentrations were compared. A range of different bone types was compared and showed that the concentration is strongly dependent on the bone type. In concordance with previous publications, the humerus shows the highest drug levels. Skeletal tissue concentrations found ranged from 1.1 to 587.8 ng/g. Comparison of the same bone type between the different rats showed high variances. However, the drugs−metabolite ratio proved to have lower variances (<20%). Moreover, the drugs−metabolite ratio in the sampled bones is in close concordance to the ratios seen in blood within a rat. From this, we can assume that the drugs−metabolite ratio in skeletal tissue may prove to be more useful than absolute found concentration.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats

Vandenbosch

Somers

Cuypers

2019

Drug Testing and Analysis

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“…In this case study, a specimen of shaft from the left thigh bone of a postmortem case was analyzed by an UHPLC‐MS/MS method, developed by our group and capable of the unambiguous identification and quantification of 27 drugs. The sample pretreatment was simple, and the developed UHPLC‐MS/MS method was accurate and precise for the drug analysis of human bone samples.…”

mentioning

confidence: 99%

Alprazolam and Zolpidem in Skeletal Tissue of Decomposed Body Confirms Exposure

Orfanidis

Gika

Zaggelidou³

et al. 2018

Journal of Forensic Sciences

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In several medico-legal cases, bone samples analysis may provide the only source of toxicological information. This case study reports the analysis of a human bone specimen, belonging to a 46-year-old man, found 3 months after his death due to cervical-thoracic injuries in a motorcycle accident. Bone specimen was the only available material for toxicological analysis, among few skull hair and rotten skin. Analysis was performed by a newly developed and validated ultra-high-pressure liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS) method, following simple and efficient sample pretreatment. The results were in accordance with the man's medical record: Alprazolam and zolpidem were found at 2.2 and 5.4 ng/g of bone, respectively. Both these drugs were prescribed to the deceased.

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Sample Collection, Transport, and Storage

2020

Fundamentals of Analytical Toxicology

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Determination of drugs of abuse and pharmaceuticals in skeletal tissue by UHPLC–MS/MS

Cited by 43 publications

References 17 publications

Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats

Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats

Alprazolam and Zolpidem in Skeletal Tissue of Decomposed Body Confirms Exposure

Sample Collection, Transport, and Storage

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