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Development of an UPLC-MS/MS method for the analysis of 16 synthetic opioids in segmented hair, and evaluation of the polydrug history in fentanyl analogue users.
Forensic Sci Int. 2020 Feb; 307:110137.FS

Abstract

Seizures of synthetic opioids have increased since 2012, with a 45 % increase in synthetic opioid related deaths between 2016 and 2017 in US. Recently, concerns have arisen around these substances and their illicit use also in several European countries. Our aim was to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of 16 synthetic opioids in segmented hair, including fentanyl, norfentanyl, acetylfentanyl, U-47700, AH-7921, acrylfentanyl, crotonylfentanyl, butyrylfentanyl, methoxacetylfentanyl, U-49900, valeryfentanyl, 4-fluoro-iso-butyrylfentanyl, ocfentanyl, furanylfentanyl, tetrahydrofuranylfentanyl, and alfetanyl. Sample preparation involved washing the hair in dichloromethane, water and methanol, and extraction in methanol, followed by solid phase extraction clean-up. This method was validated for linearity, limit of quantification (LLOQ), precision and bias, selectivity, stability, matrix effects, extraction efficiency of the clean up procedure, and carryover. LLOQs ranged from 0.15-1pg/mg, and the calibration ranged from the LLOQ up to 500pg/mg. Intra and inter-day precision were evaluated at low and high concentrations, with spiked QCs, during 8 days and the results were satisfactory with RSD<15 % for all the compounds except for norfentanyl (22 %) and alfentanyl (19 %). Two external certified QCs containing fentanyl at 11 and 105pg/mg were also analysed within each batch and the RSD and bias were lower than 16 % and 10 %, respectively. Matrix effects compensated by internal standard fentanyl-d5 (MEIS), were between 77-115 % (RSD<10 %) and extraction efficiency of the clean-up procedure was between 66-93 % (RSD<21 %). Processed sample stability and carryover were acceptable for all of the compounds. The method was applied to 17 authentic hair samples (body or head hair) from US fentanyl analogue users. When head hair was available, the hair strands were analysed in 1cm/segment. Concentrations ranges were as follows: fentanyl (n=16) 2->ULOQ (500) pg/mg, norfentanyl (n=14) 1-38pg/mg, acetylfentanyl (n=7) 0.6->ULOQ (250) pg/mg, furanylfentanyl (n=5) 2-123pg/mg, tetrahydrofuranylfentanyl (n=1) 0.5-63pg/mg and valerylfentanyl (n=1) 2.1->ULOQ (50) pg/mg, along the hair strands. To our knowledge, this is the first time where concentrations of tetrahydrofuranylfentanyl, and valerylfentanyl in hair are reported. The same samples were also analysed for the determination of other drugs of abuse using our routine method (also in 1cm/segment for head hair when available). The results demonstrated poly-drug use in these fentanyl-analogue users population (mean drugs: n=5): amphetamine and/or methamphetamine (n=10), buprenorphine (n=5), cocaine (n=8), methadone (n=8), 6-MAM (n=17), meperidine (n=1), oxycodone (n=11), tramadol (n=3). Evaluation of the concentrations of these drugs, together with the fentanyl analogues is discussed in the present paper. Two authentic samples from two Belgian post-mortem cases, were also analysed showing fentanyl use and in one case polydrug use. The results demonstrated multi-analyte quantitative methods, including fentanyl analogues, are becoming useful in forensic laboratories involved in hair analysis, and in particular when polydrug use is suspected.

Authors+Show Affiliations

Federal Public Service Justice, National Institute of Criminalistics and Criminology, Brussels, Belgium. Electronic address: mariadelmar.ramirezfernandez@just.fgov.be.Federal Public Service Justice, National Institute of Criminalistics and Criminology, Brussels, Belgium.King's College London, Department of Analytical, Environmental and Forensic Sciences, London, UK.Psychemedics Corporation, Culver City, CA, USA.Federal Public Service Justice, National Institute of Criminalistics and Criminology, Brussels, Belgium.

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

31927248

Citation

Ramírez Fernández, María Del Mar, et al. "Development of an UPLC-MS/MS Method for the Analysis of 16 Synthetic Opioids in Segmented Hair, and Evaluation of the Polydrug History in Fentanyl Analogue Users." Forensic Science International, vol. 307, 2020, p. 110137.
Ramírez Fernández MDM, Wille SMR, Jankowski D, et al. Development of an UPLC-MS/MS method for the analysis of 16 synthetic opioids in segmented hair, and evaluation of the polydrug history in fentanyl analogue users. Forensic Sci Int. 2020;307:110137.
Ramírez Fernández, M. D. M., Wille, S. M. R., Jankowski, D., Hill, V., & Samyn, N. (2020). Development of an UPLC-MS/MS method for the analysis of 16 synthetic opioids in segmented hair, and evaluation of the polydrug history in fentanyl analogue users. Forensic Science International, 307, 110137. https://doi.org/10.1016/j.forsciint.2019.110137
Ramírez Fernández MDM, et al. Development of an UPLC-MS/MS Method for the Analysis of 16 Synthetic Opioids in Segmented Hair, and Evaluation of the Polydrug History in Fentanyl Analogue Users. Forensic Sci Int. 2020;307:110137. PubMed PMID: 31927248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of an UPLC-MS/MS method for the analysis of 16 synthetic opioids in segmented hair, and evaluation of the polydrug history in fentanyl analogue users. AU - Ramírez Fernández,María Del Mar, AU - Wille,Sarah M R, AU - Jankowski,Danielle, AU - Hill,Virginia, AU - Samyn,Nele, Y1 - 2019/12/31/ PY - 2019/10/18/received PY - 2019/12/12/revised PY - 2019/12/23/accepted PY - 2020/1/14/pubmed PY - 2020/2/11/medline PY - 2020/1/14/entrez KW - Fentanyl analogues KW - Hair KW - NPS KW - Poly-drug use KW - UPLC-MS/MS KW - Validation SP - 110137 EP - 110137 JF - Forensic science international JO - Forensic Sci Int VL - 307 N2 - Seizures of synthetic opioids have increased since 2012, with a 45 % increase in synthetic opioid related deaths between 2016 and 2017 in US. Recently, concerns have arisen around these substances and their illicit use also in several European countries. Our aim was to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of 16 synthetic opioids in segmented hair, including fentanyl, norfentanyl, acetylfentanyl, U-47700, AH-7921, acrylfentanyl, crotonylfentanyl, butyrylfentanyl, methoxacetylfentanyl, U-49900, valeryfentanyl, 4-fluoro-iso-butyrylfentanyl, ocfentanyl, furanylfentanyl, tetrahydrofuranylfentanyl, and alfetanyl. Sample preparation involved washing the hair in dichloromethane, water and methanol, and extraction in methanol, followed by solid phase extraction clean-up. This method was validated for linearity, limit of quantification (LLOQ), precision and bias, selectivity, stability, matrix effects, extraction efficiency of the clean up procedure, and carryover. LLOQs ranged from 0.15-1pg/mg, and the calibration ranged from the LLOQ up to 500pg/mg. Intra and inter-day precision were evaluated at low and high concentrations, with spiked QCs, during 8 days and the results were satisfactory with RSD<15 % for all the compounds except for norfentanyl (22 %) and alfentanyl (19 %). Two external certified QCs containing fentanyl at 11 and 105pg/mg were also analysed within each batch and the RSD and bias were lower than 16 % and 10 %, respectively. Matrix effects compensated by internal standard fentanyl-d5 (MEIS), were between 77-115 % (RSD<10 %) and extraction efficiency of the clean-up procedure was between 66-93 % (RSD<21 %). Processed sample stability and carryover were acceptable for all of the compounds. The method was applied to 17 authentic hair samples (body or head hair) from US fentanyl analogue users. When head hair was available, the hair strands were analysed in 1cm/segment. Concentrations ranges were as follows: fentanyl (n=16) 2->ULOQ (500) pg/mg, norfentanyl (n=14) 1-38pg/mg, acetylfentanyl (n=7) 0.6->ULOQ (250) pg/mg, furanylfentanyl (n=5) 2-123pg/mg, tetrahydrofuranylfentanyl (n=1) 0.5-63pg/mg and valerylfentanyl (n=1) 2.1->ULOQ (50) pg/mg, along the hair strands. To our knowledge, this is the first time where concentrations of tetrahydrofuranylfentanyl, and valerylfentanyl in hair are reported. The same samples were also analysed for the determination of other drugs of abuse using our routine method (also in 1cm/segment for head hair when available). The results demonstrated poly-drug use in these fentanyl-analogue users population (mean drugs: n=5): amphetamine and/or methamphetamine (n=10), buprenorphine (n=5), cocaine (n=8), methadone (n=8), 6-MAM (n=17), meperidine (n=1), oxycodone (n=11), tramadol (n=3). Evaluation of the concentrations of these drugs, together with the fentanyl analogues is discussed in the present paper. Two authentic samples from two Belgian post-mortem cases, were also analysed showing fentanyl use and in one case polydrug use. The results demonstrated multi-analyte quantitative methods, including fentanyl analogues, are becoming useful in forensic laboratories involved in hair analysis, and in particular when polydrug use is suspected. SN - 1872-6283 UR - https://www.unboundmedicine.com/medline/citation/31927248/Development_of_an_UPLC_MS/MS_method_for_the_analysis_of_16_synthetic_opioids_in_segmented_hair_and_evaluation_of_the_polydrug_history_in_fentanyl_analogue_users_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0379-0738(19)30549-3 DB - PRIME DP - Unbound Medicine ER -