Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions

Rubin Gulaboski, M. Natalia D. S. Cordeiro, Nuno Milhazes, Jorge Garrido, Fernanda Borges, Miguel Jorge, Carlos M. Pereira, Ivan Bogeski, Aluska Helguera Morales, Blaze Naumoski, A. Fernando Silva

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

For the first time, the partition coefficients of the ionized forms of several opioids, amphetamine-like drugs, and their metabolites were determined by studying their ionic transfer process across the bare interface water/organic solvent. The ionic partition coefficients of the monocationic forms of 12 compounds heroin, 6-monoacetylmorphine (6-MAM), morphine, acetylcodeine, codeine, dihydrocodeine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), 3,4-methylenedioxyamphetamine (MDA), 3-methoxy-alpha-methyldopamine (3-OMe-alpha-MeDA), and alpha-methyldopamine (alpha-MeDA)-were attained using electrochemical measurements, by cyclic voltammetry, at the interface between two immiscible electrolyte solutions (ITIES). Then the acquired lipophilicity values were correlated to the chemical structure of the compounds and with the metabolic pathways central to each class of drugs. Although the mechanisms of biotoxicity of this type of drugs are still unclear, the data obtained evidence that the lipophilicity of metabolites may be a contributing factor for the qualitative differences found in their activity. In addition, the partition coefficients of the ionic drugs were calculated using three available software packages: ModesLab, Dragon, and HyperChem. As shown by cross-comparison of the experimental and calculated values, HyperChem was the most reliable software for achieving the main goal. The data obtained so far seem to be correlated to the proposed metabolic pathways of the drugs and could be of great value in understanding their pharmacological and/or toxicological profiles at the molecular level. This study may also contribute to gaining an insight into the mechanisms of biotransportation of this type of compounds given that the ionic partition coefficients reflect their ability to cross the membrane barriers. (c) 2006 Elsevier Inc. All rights reserved.

LanguageEnglish
Pages236-243
Number of pages8
JournalAnalytical Biochemistry
Volume361
Issue number2
DOIs
Publication statusPublished - 15 Feb 2007

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Amphetamine
Metabolites
Opioid Analgesics
N-Methyl-3,4-methylenedioxyamphetamine
Ionic drugs
Pharmaceutical Preparations
Metabolic Networks and Pathways
3,4-Methylenedioxyamphetamine
Codeine
Software
Methamphetamine
Heroin
Software packages
Organic solvents
Morphine
Electrolytes
Cyclic voltammetry
Toxicology
Membranes
Water

Keywords

  • opioids
  • amphetamine-like drugs
  • metabolites
  • partition coefficients
  • ion transfer

Cite this

Gulaboski, Rubin ; Cordeiro, M. Natalia D. S. ; Milhazes, Nuno ; Garrido, Jorge ; Borges, Fernanda ; Jorge, Miguel ; Pereira, Carlos M. ; Bogeski, Ivan ; Morales, Aluska Helguera ; Naumoski, Blaze ; Silva, A. Fernando. / Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions. In: Analytical Biochemistry. 2007 ; Vol. 361, No. 2. pp. 236-243.
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Gulaboski, R, Cordeiro, MNDS, Milhazes, N, Garrido, J, Borges, F, Jorge, M, Pereira, CM, Bogeski, I, Morales, AH, Naumoski, B & Silva, AF 2007, 'Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions' Analytical Biochemistry, vol. 361, no. 2, pp. 236-243. https://doi.org/10.1016/j.ab.2006.11.006

Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions. / Gulaboski, Rubin; Cordeiro, M. Natalia D. S.; Milhazes, Nuno; Garrido, Jorge; Borges, Fernanda; Jorge, Miguel; Pereira, Carlos M.; Bogeski, Ivan; Morales, Aluska Helguera; Naumoski, Blaze; Silva, A. Fernando.

In: Analytical Biochemistry, Vol. 361, No. 2, 15.02.2007, p. 236-243.

Research output: Contribution to journalArticle

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T1 - Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions

AU - Gulaboski, Rubin

AU - Cordeiro, M. Natalia D. S.

AU - Milhazes, Nuno

AU - Garrido, Jorge

AU - Borges, Fernanda

AU - Jorge, Miguel

AU - Pereira, Carlos M.

AU - Bogeski, Ivan

AU - Morales, Aluska Helguera

AU - Naumoski, Blaze

AU - Silva, A. Fernando

PY - 2007/2/15

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N2 - For the first time, the partition coefficients of the ionized forms of several opioids, amphetamine-like drugs, and their metabolites were determined by studying their ionic transfer process across the bare interface water/organic solvent. The ionic partition coefficients of the monocationic forms of 12 compounds heroin, 6-monoacetylmorphine (6-MAM), morphine, acetylcodeine, codeine, dihydrocodeine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), 3,4-methylenedioxyamphetamine (MDA), 3-methoxy-alpha-methyldopamine (3-OMe-alpha-MeDA), and alpha-methyldopamine (alpha-MeDA)-were attained using electrochemical measurements, by cyclic voltammetry, at the interface between two immiscible electrolyte solutions (ITIES). Then the acquired lipophilicity values were correlated to the chemical structure of the compounds and with the metabolic pathways central to each class of drugs. Although the mechanisms of biotoxicity of this type of drugs are still unclear, the data obtained evidence that the lipophilicity of metabolites may be a contributing factor for the qualitative differences found in their activity. In addition, the partition coefficients of the ionic drugs were calculated using three available software packages: ModesLab, Dragon, and HyperChem. As shown by cross-comparison of the experimental and calculated values, HyperChem was the most reliable software for achieving the main goal. The data obtained so far seem to be correlated to the proposed metabolic pathways of the drugs and could be of great value in understanding their pharmacological and/or toxicological profiles at the molecular level. This study may also contribute to gaining an insight into the mechanisms of biotransportation of this type of compounds given that the ionic partition coefficients reflect their ability to cross the membrane barriers. (c) 2006 Elsevier Inc. All rights reserved.

AB - For the first time, the partition coefficients of the ionized forms of several opioids, amphetamine-like drugs, and their metabolites were determined by studying their ionic transfer process across the bare interface water/organic solvent. The ionic partition coefficients of the monocationic forms of 12 compounds heroin, 6-monoacetylmorphine (6-MAM), morphine, acetylcodeine, codeine, dihydrocodeine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), 3,4-methylenedioxyamphetamine (MDA), 3-methoxy-alpha-methyldopamine (3-OMe-alpha-MeDA), and alpha-methyldopamine (alpha-MeDA)-were attained using electrochemical measurements, by cyclic voltammetry, at the interface between two immiscible electrolyte solutions (ITIES). Then the acquired lipophilicity values were correlated to the chemical structure of the compounds and with the metabolic pathways central to each class of drugs. Although the mechanisms of biotoxicity of this type of drugs are still unclear, the data obtained evidence that the lipophilicity of metabolites may be a contributing factor for the qualitative differences found in their activity. In addition, the partition coefficients of the ionic drugs were calculated using three available software packages: ModesLab, Dragon, and HyperChem. As shown by cross-comparison of the experimental and calculated values, HyperChem was the most reliable software for achieving the main goal. The data obtained so far seem to be correlated to the proposed metabolic pathways of the drugs and could be of great value in understanding their pharmacological and/or toxicological profiles at the molecular level. This study may also contribute to gaining an insight into the mechanisms of biotransportation of this type of compounds given that the ionic partition coefficients reflect their ability to cross the membrane barriers. (c) 2006 Elsevier Inc. All rights reserved.

KW - opioids

KW - amphetamine-like drugs

KW - metabolites

KW - partition coefficients

KW - ion transfer

U2 - 10.1016/j.ab.2006.11.006

DO - 10.1016/j.ab.2006.11.006

M3 - Article

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JO - Analytical Biochemistry

T2 - Analytical Biochemistry

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