Elucidation of the Phase I and Phase II metabolic pathways of (±)-4'-methylmethcathinone (4-MMC) and (±)-4'-(trifluoromethyl)methcathinone (4-TFMMC) in rat liver hepatocytes using LC-MS and LC-MS2

Journal of Pharmaceutical and Biomedical Analysis

Volumn 72, Issue , 2013, Pages 177-185

  Khreit, Osama I G ^a   Grant, M Helen ^a   Zhang, Tong ^a   Henderson, Catherine ^a   Watson, David G ^a   Sutcliffe, Oliver B ^a,b  

^a UNIVERSITY OF STRATHCLYDE   (United Kingdom)

^b MANCHESTER METROPOLITAN UNIVERSITY   (United Kingdom)

Author keywords

4 MMC; 4 TFMMC; Cathinone; Mass spectrometry; Metabolism; ZIC HILIC

Indexed keywords

4' (TRIFLUOROMETHYL)METHCATHINONE; 4' METHYLMETHCATHINONE; AMPHOLYTE; CATHINONE; DRUG METABOLITE; METHCATHINONE; UNCLASSIFIED DRUG;

ACCURACY; ANALYTIC METHOD; ANIMAL CELL; ARTICLE; BIOTRANSFORMATION; CHEMICAL MODIFICATION; HALF LIFE TIME; HYDROPHILICITY; IN VITRO STUDY; IN VIVO STUDY; LIQUID CHROMATOGRAPHY; LIQUID CHROMATOGRAPHY MASS SPECTROMETRY; LIQUID CHROMATOGRAPHY MASS SPECTROMETRY MASS SPECTROMETRY; LIVER CELL; MASS SPECTROMETRY; METABOLISM; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RAT; REDUCTION;

ANIMALS; BIOTRANSFORMATION; CELL SURVIVAL; CHROMATOGRAPHY, LIQUID; HEPATOCYTES; LIVER; MALE; MASS SPECTROMETRY; METABOLIC DETOXICATION, PHASE I; METABOLIC DETOXICATION, PHASE II; METHAMPHETAMINE; OXIDATION-REDUCTION; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84869096843     PISSN: 07317085     EISSN: 1873264X     Source Type: Journal    
DOI: 10.1016/j.jpba.2012.08.015     Document Type: Article

References (24)

1. Hillebrand J., Olszewski D., Sedefov R. Legal highs on the Internet. Subst. Use Misuse 2010, 45:330-340.
2. Kelly J.P. Cathinone derivatives: a review of their chemistry pharmacology and toxicology. Drug Test. Anal. 2011, 3:439-453.
3. Camilleri A., Johnston M.R., Brennan M., Davis S., Caldicott D.G.E. Chemical analysis of four capsules containing the controlled substance analogues 4-methylmethcathinone 2-fluoromethamphetamine, alpha-phthalimidopropiophenone and N-ethylcathinone. Forensic Sci. Int. 2010, 197:59-66.
4. Santali E.Y., Cadogan A-K., Nic Daeid N., Savage K.A., Sutcliffe O.B. Synthesis full chemical characterisation and development of validated methods for the quantification of (±)-4'-methylmethcathinone (mephedrone): a new legal high. J. Pharm. Biomed. Anal. 2011, 56:246-255.
5. Schifano F., Albanese A., Fergus S., Stair J.L., Deluca P., Corazza O., Davey Z., Corkery J., Siemann H., Scherbaum N., Farre M., Torrens M., Demetrovics Z., Ghodse H.A. Mephedrone (4-methylmethcathinone; meow meow): chemical pharmacological and clinical issues. Psychopharmacology 2011, 214:593-602.
6. Brandt S.D., Freeman S., Sumnall H.R., Measham F., Cole J. Analyses of second generation legal highs in the UK: initial findings. Drug Test. Anal. 2010, 2:377-382.
7. Khreit O.I.G., Irving C., Schmidt E., Parkinson J.A., Nic Daeid N., Sutcliffe O.B. Synthesis full chemical characterisation and development of validated methods for the quantification of the components found in the evolved legal high NRG-2. J. Pharm. Biomed. Anal. 2012, 61:122-135.
8. Dargan P.I., Sedefov R., Gallegos A., Wood D.M. The pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone). Drug Test. Anal. 2011, 3:464-465.
9. Dickson A.J., Vorce S.P., Levine B., Past M.R. Multiple-drug toxicity caused by the coadministration of 4-methylmethcathinone (mephedrone) and heroin. J. Anal. Toxicol. 2010, 34:162-168.
10. Wood D.M., Davis S., Puchnarewicz M., Button J., Archer R., Ovaska H., Ramsey J., Lee T., Holt D.W., Dargan P.I. Recreational use of mephedrone (4-methylmethcathinone 4-MMC) with associated sympathomimetic toxicity. J. Med. Toxicol. 2010, 6:327-330.
11. Wood D.M., Davis S., Greene S.L., Button J., Holt D.W., Ramsey J., Dargan P.I. Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin. Toxicol. 2010, 48:924-927.
12. Maskell P.D., De Paoli G., Seneviratne C., Pounder D.J. Mephedrone (4-methylmethcathinone)-related deaths. J. Anal. Toxicol. 2011, 35:188-191.
13. Torrance H., Cooper G. The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland. Forensic Sci. Int. 2010, 202:e62.
14. Meyer M.R., Wilhelm J., Peters F.T., Maurer H.H. Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal. Bioanal. Chem. 2010, 396:1225-1233.
15. Meyer M.R., Maurer H.H. Metabolism of designer drugs of abuse: an updated review. Curr. Drug Metab. 2010, 11:468-482.
16. A.J. Pedersen, L.A. Reitzel, S.S. Johansen, K. Linnet, In vitro metabolism studies on mephedrone and analysis of forensic cases. Drug Test. Anal. doi:10.1002/dta.1369.
17. Meyer M.R., Vollmar C., Schwaninger A.E., Wolf E., Maurer H.H. New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine. J. Mass Spectrom. 2012, 47:253-262.
18. S.D. Brandt, P.F. Daley, N.V. Cozzi, Analytical characterization of three trifluoromethyl-substituted methcathinone isomers. Drug Test. Anal. doi:10.1002/dta.382.
19. Kalendra D.M., Sickles B.R. Diminished reactivity of ortho-substituted phenacyl bromides toward nucleophilic displacement. J. Org. Chem. 2003, 68:1594-1596.
20. Moldeus P., Hoegberg J., Orrenius S. Methods in Enzymology 1978, Academic Press, New York, pp. 60-71. S. Fleischer, L. Packer (Eds.).
21. Hayward M., Bacolod M.D., Han Q.P., Cajina M., Zou Z. Techniques to Facilitate the Performance of Mass Spectrometry: Sample Preparation, Liquid Chromatography, and Non-mass-spectrometric Detection in Mass Spectrometry in Drug Metabolism and Disposition: Basic Principles and Applications 2011, 353-381. John Wiley and Sons, Inc., New York. M.S. Lee, M. Zhu (Eds.).
22. Creek D.J., Jankevics A., Breitling R., Watson D.G., Barrett M.P., Burgess K.E.V. Toward global metabolomics analysis with hydrophilic interaction liquid chromatography-mass spectrometry: improved metabolite identification by retention time prediction. Anal. Chem. 2011, 83:8703-8710.
23. Gibson G.G., Skett P. Introduction to Drug Metabolism 2001, Nelson Thomas, London, pp. 204-214.
24. Gibson G.G., Skett P. Introduction to Drug Metabolism 2001, Nelson Thomas, London, pp. 196-197.