Öz
Introduction: Illicit drug use is an ever-increasing problem all over the world also reflected in emergency services as drug-induced toxicities. There is limited data about illicit drugs that pose pediatric emergency cases in our country which of most are based on immunochemical screening test results that are prone to false positivity and negativity or insufficient for some drugs.
Materials and methods: We established validated LC-MS/MS methods for 39 illicit drug analytes and used them to evaluate blood and urine samples of pediatric emergency patients (n=50, mean age: 15.9 y, 72% male; %28 female) along with an easy and short sample preparation step.
Results: Acceptable method validation results by means of linearity, repeatability, accuracy, sensitivity, and selectivity were achieved. Illicit drugs were detected in 60% of patients, of these 71.4% were male, and 40% of patients showed mixed drugs. Amphetamine-type drugs and synthetic cathinones were the most found illegal drugs in samples.
Conclusion: This study was the first to use LC-MS/MS for the determination of 39 illicit drug analytes in pediatric emergency patients in our country. LC-MS/MS is a reliable, sensitive tool for the evaluation of drug-suspected emergency patients. In particular, drug use profiles that cause urgent health problems should be kept up-to-date and shared through a national network so that physicians and toxicologists, as well as officials who make regulations on illicit drug policy, should be informed.
Anahtar Kelimeler
Illicit drug Pediatric emergency Liquid chromatography-tandem mass spectrometry Method development
Destekleyen Kurum
Hacettepe University Scientific Research Unit
Proje Numarası
THD-2016-9803
Teşekkür
We thank the Forensic Toxicology Laboratory staff at Hacettepe University Hospitals for their support during the laboratory works. We also thank Dr. Ümmü Aydoğmuş and Dr. Aykut Lale for helping us to collect the samples and questionnaires from the patients.
Kaynakça
- 1. EMCDDA. European Drug Report 2018. 2018.
- 2. EMCDDA. European drug report 2015. 2015.
- 3. Klaus L, Nociar, A. ESPAD Report 2015 - Results from the European School Survey Project on Alcohol and Other Drugs. 2016:99.
- 4. Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol (Phila). 2016;54(1):1-13.
- 5. Richards JR, Garber D, Laurin EG, Albertson TE, Derlet RW, Amsterdam EA, et al. Treatment of cocaine cardiovascular toxicity: a systematic review. Clin Toxicol (Phila). 2016;54(5):345-64.
- 6. Swepson C, Ranjan A, Balasubramaniam M, Pandhare J, Dash C. Cocaine Enhances HIV-1 Transcription in Macrophages by Inducing p38 MAPK Phosphorylation. Front Microbiol. 2016;7:823.
- 7. Paratz ED, Cunningham NJ, MacIsaac AI. The Cardiac Complications of Methamphetamines. Heart Lung Circ. 2016;25(4):325-32.
- 8. Sanchez-Ramos J. Neurologic Complications of Psychomotor Stimulant Abuse. Int Rev Neurobiol. 2015;120:131-60.
- 9. Shelton CP, Rosini JM. Multisystem Organ Failure and Death Resulting From Ingestion of "Molly" (3,4-Methylenedioxymethamphetamine). J Emerg Nurs. 2015;41(5):447-50.
- 10. EMCDDA. European Drug Report 2019. 2019.
- 11. Saitman A, Park H-D, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. Journal of analytical toxicology. 2014;38(7):387-96.
- 12. Van Wijk XM, Goodnough R, Colby JM. Mass spectrometry in emergency toxicology: Current state and future applications. Critical reviews in clinical laboratory sciences. 2019;56(4):225-38.
- 13. Toxicology SWGfF. Scientific Working Group for Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. Journal of Analytical Toxicology. 2013;37(7):452-74.
- 14. Ministry, of, Health. The Working Procedures and Principles of Confirmation Laboratories. Official Gazette of Republic of Turkey. 2015 (Circular 14).
- 15. Knittel JL, Holler JM, Chmiel JD, Vorce SP, Magluilo J, Jr., Levine B, et al. Analysis of Parent Synthetic Cannabinoids in Blood and Urinary Metabolites by Liquid Chromatography Tandem Mass Spectrometry. J Anal Toxicol. 2016;40(3):173-86.
- 16. Jang M, Shin I, Kim J, Yang W. Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry. Forensic Toxicology. 2015;33(2):221-34.
- 17. Marinetti LJ, Antonides HM. Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results. J Anal Toxicol. 2013;37(3):135-46.
- 18. Yang HS, Wu AH, Lynch KL. Development and Validation of a Novel LC-MS/MS Opioid Confirmation Assay: Evaluation of beta-glucuronidase Enzymes and Sample Cleanup Methods. J Anal Toxicol. 2016;40(5):323-9.
- 19. Schaefer N, Peters B, Schmidt P, Ewald AH. Development and validation of two LC-MS/MS methods for the detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine using turbulent flow chromatography. Analytical and bioanalytical chemistry. 2013;405(1):247-58.
- 20. Berg T, Lundanes E, Christophersen AS, Strand DH. Determination of opiates and cocaine in urine by high pH mobile phase reversed phase UPLC–MS/MS. Journal of Chromatography B. 2009;877(4):421-32.
- 21. Scheidweiler KB, Desrosiers NA, Huestis MA. Simultaneous quantification of free and glucuronidated cannabinoids in human urine by liquid chromatography tandem mass spectrometry. Clinica chimica acta. 2012;413(23-24):1839-47.
- 22. Ammann D, McLaren JM, Gerostamoulos D, Beyer J. Detection and Quantification of New Designer Drugs in Human Blood: Part 2 Designer Cathinones. Journal of Analytical Toxicology. 2012;36(6):381-9.
- 23. Wohlfarth A, Scheidweiler KB, Chen XH, Liu HF, Huestis MA. Qualitative Confirmation of 9 Synthetic Cannabinoids and 20 Metabolites in Human Urine Using LC-MS/MS and Library Search. Anal Chem. 2013;85(7):3730-8.
- 24. Coles R, Kushnir MM, Nelson GJ, McMillin GA, Urry FM. Simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine in urine, serum, plasma, whole blood, and meconium by LC-MS-MS. Journal of Analytical Toxicology. 2007;31(1):1-14.
- 25. Jimenez C, De la Torre R, Ventura M, Segura J, Ventura R. Stability studies of amphetamine and ephedrine derivatives in urine. Journal of Chromatography B. 2006;843(1):84-93.
- 26. Clauwaert KM, Van Bocxlaer JF, De Leenheer AP. Stability study of the designer drugs “MDA, MDMA and MDEA” in water, serum, whole blood, and urine under various storage temperatures. Forensic science international. 2001;124(1):36-42.
- 27. Kozer E, Bar-Hamburger R, Rosenfeld NY, Zdanovitch I, Bulkowstein M, Berkovitch M. Illicit drug and alcohol users admitted to the pediatric emergency department. Age (yrs, median and range). 2008;16:12-8.
- 28. Fahimi J, Aurrecoechea A, Anderson E, Herring A, Alter H. Substance abuse and mental health visits among adolescents presenting to US emergency departments. Pediatric emergency care. 2015;31(5):331.
- 29. Forrester MB. Adolescent synthetic cathinone exposures reported to Texas poison centers. Pediatric emergency care. 2013;29(2):151-5.
- 30. Jalali R, Dmochowska P, Godlewska I, Balmas J, Młynarska K, Narkun K, et al. Designers Drugs—A New Challenge to Emergency Departments—An Observational Study in Poland. Medicina. 2020;56(7):354.
Öz
Giriş: Yasa dışı madde kullanımı, tüm dünyada giderek artan bir sorun olup, uyuşturucu kaynaklı toksisiteler olarak acil servislere de yansımaktadır. Ülkemizde yasa dışı uyuşturuculara bağlı çocuk acil vaka verileri sınırlı sayıda olup bunların çoğu da yanlış pozitif ve negatif sonuç verme ihtimali olan veya bazı ilaçlar için yetersiz olan immünokimyasal tarama testlerine dayalı verilerdir.
Gereç ve yöntemler: Otuz dokuz yasa dışı uyuşturucu analiti için valide edilmiş LC-MS/MS yöntemleri oluşturduk ve kolay ve kısa bir numune hazırlama aşamasından sonra çocuk acil hastalarının (n=50, ortalama yaş: 15,9 y, %72 erkek; %28 kadın) kan ve idrar örneklerini değerlendirmek için kullandık.
Bulgular: Doğrusallık, tekrarlanabilirlik, doğruluk, duyarlılık ve seçicilik paramenlerinde kabul edilebilir yöntem doğrulama sonuçları elde edildi. Hastaların %60'ında yasa dışı uyuşturucu madde tespit edildi, bunların %71,4'ü erkekti ve hastaların %40'ında çoklu uyuşturucu madde görüldü. Amfetamin türü uyuşturucular ve sentetik katinonlar, örneklerde en fazla bulunan yasa dışı uyuşturuculardı.
Sonuç: Bu çalışma, ülkemizde, çocuk acil hastalarında 39 yasa dışı uyuşturucu madde analitinin araştırılması için LC-MS/MS kullanılan ilk çalışmadır. LC-MS/MS, uyuşturucudan şüphelenilen acil hastaların değerlendirilmesi için güvenilir, hassas bir araçtır. Özellikle acil sağlık sorunlarına neden olan ilaç kullanım profilleri güncel tutulmalı ve ulusal bir ağ üzerinden paylaşılarak hekim ve toksikologların yanı sıra yasa dışı ilaç politikası ile ilgili düzenlemeleri yapan yetkililerin bilgilendirilmesi sağlanmalıdır.
Anahtar Kelimeler
Yasadışı uyuşturucu Çocuk acil Sıvı kromatografisi-tandem kütle spektrometrisi Metot geliştirme
Proje Numarası
THD-2016-9803
Kaynakça
- 1. EMCDDA. European Drug Report 2018. 2018.
- 2. EMCDDA. European drug report 2015. 2015.
- 3. Klaus L, Nociar, A. ESPAD Report 2015 - Results from the European School Survey Project on Alcohol and Other Drugs. 2016:99.
- 4. Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol (Phila). 2016;54(1):1-13.
- 5. Richards JR, Garber D, Laurin EG, Albertson TE, Derlet RW, Amsterdam EA, et al. Treatment of cocaine cardiovascular toxicity: a systematic review. Clin Toxicol (Phila). 2016;54(5):345-64.
- 6. Swepson C, Ranjan A, Balasubramaniam M, Pandhare J, Dash C. Cocaine Enhances HIV-1 Transcription in Macrophages by Inducing p38 MAPK Phosphorylation. Front Microbiol. 2016;7:823.
- 7. Paratz ED, Cunningham NJ, MacIsaac AI. The Cardiac Complications of Methamphetamines. Heart Lung Circ. 2016;25(4):325-32.
- 8. Sanchez-Ramos J. Neurologic Complications of Psychomotor Stimulant Abuse. Int Rev Neurobiol. 2015;120:131-60.
- 9. Shelton CP, Rosini JM. Multisystem Organ Failure and Death Resulting From Ingestion of "Molly" (3,4-Methylenedioxymethamphetamine). J Emerg Nurs. 2015;41(5):447-50.
- 10. EMCDDA. European Drug Report 2019. 2019.
- 11. Saitman A, Park H-D, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. Journal of analytical toxicology. 2014;38(7):387-96.
- 12. Van Wijk XM, Goodnough R, Colby JM. Mass spectrometry in emergency toxicology: Current state and future applications. Critical reviews in clinical laboratory sciences. 2019;56(4):225-38.
- 13. Toxicology SWGfF. Scientific Working Group for Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. Journal of Analytical Toxicology. 2013;37(7):452-74.
- 14. Ministry, of, Health. The Working Procedures and Principles of Confirmation Laboratories. Official Gazette of Republic of Turkey. 2015 (Circular 14).
- 15. Knittel JL, Holler JM, Chmiel JD, Vorce SP, Magluilo J, Jr., Levine B, et al. Analysis of Parent Synthetic Cannabinoids in Blood and Urinary Metabolites by Liquid Chromatography Tandem Mass Spectrometry. J Anal Toxicol. 2016;40(3):173-86.
- 16. Jang M, Shin I, Kim J, Yang W. Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry. Forensic Toxicology. 2015;33(2):221-34.
- 17. Marinetti LJ, Antonides HM. Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results. J Anal Toxicol. 2013;37(3):135-46.
- 18. Yang HS, Wu AH, Lynch KL. Development and Validation of a Novel LC-MS/MS Opioid Confirmation Assay: Evaluation of beta-glucuronidase Enzymes and Sample Cleanup Methods. J Anal Toxicol. 2016;40(5):323-9.
- 19. Schaefer N, Peters B, Schmidt P, Ewald AH. Development and validation of two LC-MS/MS methods for the detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine using turbulent flow chromatography. Analytical and bioanalytical chemistry. 2013;405(1):247-58.
- 20. Berg T, Lundanes E, Christophersen AS, Strand DH. Determination of opiates and cocaine in urine by high pH mobile phase reversed phase UPLC–MS/MS. Journal of Chromatography B. 2009;877(4):421-32.
- 21. Scheidweiler KB, Desrosiers NA, Huestis MA. Simultaneous quantification of free and glucuronidated cannabinoids in human urine by liquid chromatography tandem mass spectrometry. Clinica chimica acta. 2012;413(23-24):1839-47.
- 22. Ammann D, McLaren JM, Gerostamoulos D, Beyer J. Detection and Quantification of New Designer Drugs in Human Blood: Part 2 Designer Cathinones. Journal of Analytical Toxicology. 2012;36(6):381-9.
- 23. Wohlfarth A, Scheidweiler KB, Chen XH, Liu HF, Huestis MA. Qualitative Confirmation of 9 Synthetic Cannabinoids and 20 Metabolites in Human Urine Using LC-MS/MS and Library Search. Anal Chem. 2013;85(7):3730-8.
- 24. Coles R, Kushnir MM, Nelson GJ, McMillin GA, Urry FM. Simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine in urine, serum, plasma, whole blood, and meconium by LC-MS-MS. Journal of Analytical Toxicology. 2007;31(1):1-14.
- 25. Jimenez C, De la Torre R, Ventura M, Segura J, Ventura R. Stability studies of amphetamine and ephedrine derivatives in urine. Journal of Chromatography B. 2006;843(1):84-93.
- 26. Clauwaert KM, Van Bocxlaer JF, De Leenheer AP. Stability study of the designer drugs “MDA, MDMA and MDEA” in water, serum, whole blood, and urine under various storage temperatures. Forensic science international. 2001;124(1):36-42.
- 27. Kozer E, Bar-Hamburger R, Rosenfeld NY, Zdanovitch I, Bulkowstein M, Berkovitch M. Illicit drug and alcohol users admitted to the pediatric emergency department. Age (yrs, median and range). 2008;16:12-8.
- 28. Fahimi J, Aurrecoechea A, Anderson E, Herring A, Alter H. Substance abuse and mental health visits among adolescents presenting to US emergency departments. Pediatric emergency care. 2015;31(5):331.
- 29. Forrester MB. Adolescent synthetic cathinone exposures reported to Texas poison centers. Pediatric emergency care. 2013;29(2):151-5.
- 30. Jalali R, Dmochowska P, Godlewska I, Balmas J, Młynarska K, Narkun K, et al. Designers Drugs—A New Challenge to Emergency Departments—An Observational Study in Poland. Medicina. 2020;56(7):354.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Toksikoloji , Acil Tıp |
| Bölüm | Original Articles |
| Yazarlar | |
| Proje Numarası | THD-2016-9803 |
| Yayımlanma Tarihi | 31 Aralık 2022 |
| Gönderilme Tarihi | 27 Haziran 2022 |
| Yayımlandığı Sayı | Yıl 2022 Cilt: 4 Sayı: 3 |
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