Elsevier

Analytical Biochemistry

Volume 361, Issue 2, 15 February 2007, Pages 236-243
Analytical Biochemistry

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

https://doi.org/10.1016/j.ab.2006.11.006Get rights and content

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-α-methyldopamine (3-OMe-α-MeDA), and α-methyldopamine (α-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.

Section snippets

Chemicals

Morphine, codeine, and amphetamine were obtained from Uquipa and Sigma (Lisbon, Portugal) as their hydrochloride salts and were used without further purification. Dihydrocodeine bitartrate was kindly provided by Knoll Lusitana (Prior Velho, Portugal).

Acetylcodeine, heroin, 6-monoacetylmorphine (6-MAM), methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”), α-methyldopamine (α-MeDA) and 3-methoxy-α-methyldopamine (3-OMe-α-MeDA) were

Results and discussion

Drug metabolism is largely the biological process responsible for degradation of lipophilic drugs. The most relevant mechanism is their enzymatic conversion to more polar products, which have the propensity to be excreted relatively more rapidly. In general, the enzymes catalyze the biotransformation of the drugs by the following general reactions: oxidation, reduction, hydrolysis, deamination (phase I reactions), and conjugation (sulfation, glucuronation, methylation, acetylation—phase II

Conclusions

Lipophilicity and hydrogen-bonding ability are considered to be the most important physicochemical properties that rule the transmembrane movement of the drugs, whether used therapeutically or not [1], [5]. These parameters are also related to the affinity of the solute for the hydrophobic bilayer and its ability to leave the favorable hydrogen-bonding environment of the aqueous phase. Although initially it was thought that only neutral compounds were able to diffuse through biological

Acknowledgments

This work was supported by Portuguese Fundação para a Ciência e a Tecnologia (FCT) (projects POCTI/QUI/4XXX/2001, POCTI/QUI/41074/2001, and POCI/SAU-FCF/58330/2004). Rubin Gulaboski acknowledges the FCT of Portugal for the postdoctoral fellowship grant SFRH/BPD/14894/2004.

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