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Quantification of Synthetic Cathinones in Rat Brain Using HILIC-ESI-MS/MS.
J Anal Toxicol. 2016 Nov; 40(9):718-725.JA

Abstract

The abuse of synthetic cathinones, formerly marketed as "bath salts", has emerged over the last decade. Three common drugs in this class include 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). An LC-MS/MS method has been developed and validated for the simultaneous quantification of MDPV, mephedrone, and methylone in brain tissue. Briefly, MDPV, mephedrone, methylone, and their deuterium-labeled analogs were subjected to solid phase extraction (SPE) and separated using an HILIC Silica Column. The HPLC was coupled to a Shimadzu IT-TOF (ion trap-time of flight) system with the electrospray source running in positive mode (+ESI). The method was validated for precision, accuracy, and extraction efficiency. All inter-day and intra-day % RSD (percent relative standard deviation) and % error values were less than 15% and extraction efficiency exceeded 80%. These conditions allowed for limits of detection of 1ng/mL for MDPV, and 5 ng/mL for both mephedrone and methylone. The limits of quantification were determined to be 5ng/mL for MDPV and 10 ng/mL for mephedrone and methylone. The method was utilized to evaluate the pharmacokinetics of these drugs in adult male rats following administration of a drug cocktail including MDPV, mephedrone, and methylone. All three compounds reached peak concentrations in the brain within 15 min. Although methylone and mephedrone were administered at the same dose, the peak concentration (Cmax) of mephedrone in the brain was significantly higher than that for methylone, as was the area under the curve (AUC). In summary, this quick and sensitive method for measuring synthetic cathinones may be used for future pharmacokinetic investigations of these drugs in target tissue.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, East Tennessee State University Bill Gatton College of Pharmacy, Box 70594, Johnson City, TN 37614, USA.Department of Pharmaceutical Sciences, East Tennessee State University Bill Gatton College of Pharmacy, Box 70594, Johnson City, TN 37614, USA.Department of Pharmaceutical Sciences, East Tennessee State University Bill Gatton College of Pharmacy, Box 70594, Johnson City, TN 37614, USA.Department of Pharmaceutical Sciences, East Tennessee State University Bill Gatton College of Pharmacy, Box 70594, Johnson City, TN 37614, USA pond@mail.etsu.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27474358

Citation

Peters, Jacob R., et al. "Quantification of Synthetic Cathinones in Rat Brain Using HILIC-ESI-MS/MS." Journal of Analytical Toxicology, vol. 40, no. 9, 2016, pp. 718-725.
Peters JR, Keasling R, Brown SD, et al. Quantification of Synthetic Cathinones in Rat Brain Using HILIC-ESI-MS/MS. J Anal Toxicol. 2016;40(9):718-725.
Peters, J. R., Keasling, R., Brown, S. D., & Pond, B. B. (2016). Quantification of Synthetic Cathinones in Rat Brain Using HILIC-ESI-MS/MS. Journal of Analytical Toxicology, 40(9), 718-725.
Peters JR, et al. Quantification of Synthetic Cathinones in Rat Brain Using HILIC-ESI-MS/MS. J Anal Toxicol. 2016;40(9):718-725. PubMed PMID: 27474358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantification of Synthetic Cathinones in Rat Brain Using HILIC-ESI-MS/MS. AU - Peters,Jacob R, AU - Keasling,Robert, AU - Brown,Stacy D, AU - Pond,Brooks B, Y1 - 2016/07/29/ PY - 2016/06/28/received PY - 2016/05/03/revised PY - 2016/05/15/accepted PY - 2016/7/31/pubmed PY - 2017/6/20/medline PY - 2016/7/31/entrez SP - 718 EP - 725 JF - Journal of analytical toxicology JO - J Anal Toxicol VL - 40 IS - 9 N2 - The abuse of synthetic cathinones, formerly marketed as "bath salts", has emerged over the last decade. Three common drugs in this class include 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). An LC-MS/MS method has been developed and validated for the simultaneous quantification of MDPV, mephedrone, and methylone in brain tissue. Briefly, MDPV, mephedrone, methylone, and their deuterium-labeled analogs were subjected to solid phase extraction (SPE) and separated using an HILIC Silica Column. The HPLC was coupled to a Shimadzu IT-TOF (ion trap-time of flight) system with the electrospray source running in positive mode (+ESI). The method was validated for precision, accuracy, and extraction efficiency. All inter-day and intra-day % RSD (percent relative standard deviation) and % error values were less than 15% and extraction efficiency exceeded 80%. These conditions allowed for limits of detection of 1ng/mL for MDPV, and 5 ng/mL for both mephedrone and methylone. The limits of quantification were determined to be 5ng/mL for MDPV and 10 ng/mL for mephedrone and methylone. The method was utilized to evaluate the pharmacokinetics of these drugs in adult male rats following administration of a drug cocktail including MDPV, mephedrone, and methylone. All three compounds reached peak concentrations in the brain within 15 min. Although methylone and mephedrone were administered at the same dose, the peak concentration (Cmax) of mephedrone in the brain was significantly higher than that for methylone, as was the area under the curve (AUC). In summary, this quick and sensitive method for measuring synthetic cathinones may be used for future pharmacokinetic investigations of these drugs in target tissue. SN - 1945-2403 UR - https://www.unboundmedicine.com/medline/citation/27474358/Quantification_of_Synthetic_Cathinones_in_Rat_Brain_Using_HILIC_ESI_MS/MS_ L2 - https://academic.oup.com/jat/article-lookup/doi/10.1093/jat/bkw074 DB - PRIME DP - Unbound Medicine ER -