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Pharmacokinetics of Synthetic Cathinones Found in Bath Salts in Mouse Brain and Plasma Using High-Pressure Liquid Chromatography–Tandem Mass Spectrometry

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objectives

Approximately 10 years ago, “bath salts” became popular as legal alternatives to the psychostimulants cocaine and the amphetamines. These products contained synthetic cathinones, including 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). Most preclinical investigations have only assessed the effects of these synthetic cathinones independently; however, case reports and Drug Enforcement Administration (DEA) studies indicate that bath salts contain mixtures of these substances. In this study, we examine the pharmacokinetic interactions of the drug combination. We hypothesized that combined exposure to MDPV, mephedrone, and methylone would result in increased drug concentrations and enhanced total drug concentrations when compared to individual administration.

Methods

Adolescent male Swiss–Webster mice were injected intraperitoneally with either 10 mg/kg MDPV, 10 mg/kg mephedrone, 10 mg/kg methylone, or 10 mg/kg combined MDPV, mephedrone, and methylone. Following injection, brains and plasma were collected at 1, 10, 15, 30, 60, and 120 min. Drugs were extracted via solid-phase extraction, and concentrations were determined using a previously published high-pressure liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method.

Results

All drugs crossed the blood–brain barrier quickly. For methylone, the maximal concentration (Cmax) and the total drug exposure [as represented by the area under the concentration-time curve (AUC)] were significantly higher when combined with mephedrone and MDPV in both matrices (2.89-fold increase for both Cmax and AUC with combined treatment). For mephedrone, the Cmax was unchanged, but the AUC in brain was increased when in combination by approximately 34%. Interestingly, for MDPV, the Cmax was unchanged, yet the AUC was higher when MDPV was administered individually (there was a 62% decrease in AUC with combined treatment).

Conclusions

The pharmacokinetics of methylone, mepedrone, and MDPV are altered when the drugs are used in combination. These data provide insight into the consequences of co-exposure to synthetic cathinones in popular bath salt products.

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Acknowledgements

The authors would like to acknowledge Emily Perez, Greg Hanley, Angela Hanley, Hannah Oakes, and Serena Allen for their assistance in animal handling and tissue collections. The authors would also like to acknowledge and thank the East Tennessee State University Bill Gatton College of Pharmacy Department of Pharmaceutical Sciences and the Research Development Committee for their continued support of student research.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, East Tennessee State University Bill Gatton College of Pharmacy, Box 70594, Johnson City, TN, 37614, USA

    Courtney Gearlds, Jessica Brooke Bouldin, Mariah McKinney, Shannon Schreiner, Stacy D. Brown & Brooks B. Pond

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  1. Courtney Gearlds
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  2. Jessica Brooke Bouldin
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  3. Mariah McKinney
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  4. Shannon Schreiner
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  5. Stacy D. Brown
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  6. Brooks B. Pond
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Corresponding author

Correspondence to Brooks B. Pond.

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Funding

This work was funded by the Research Development Committee at East Tennessee State University and the Department of Pharmaceutical Sciences.

Conflicts of interest

Courtney Gearlds, Jessica Brooke Bouldin, Mariah McKinney, Shannon Schreiner, Stacy D. Brown, and Brooks B. Pond have no conflicts of interest to declare.

Ethics approval

Experiments and procedures with the animals were performed following the regulations set forth by the NIH Guide for the Care and Use of Laboratory Animals. The protocols followed were approved by the University Committee on Animal Care (UCAC) at East Tennessee State University (Protocol number: 190505).

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Not applicable.

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Not applicable.

Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author contributions

Data collection (CG, JBB, MM, and SS), Data analysis (SDB), funding, experimental design, data collection and analysis (BBP).

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Gearlds, C., Bouldin, J.B., McKinney, M. et al. Pharmacokinetics of Synthetic Cathinones Found in Bath Salts in Mouse Brain and Plasma Using High-Pressure Liquid Chromatography–Tandem Mass Spectrometry. Eur J Drug Metab Pharmacokinet 46, 771–778 (2021). https://doi.org/10.1007/s13318-021-00712-1

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  • DOI: https://doi.org/10.1007/s13318-021-00712-1

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