Voltammetry of naltrexone in commercial formulation and human body fluids: Quantification and pharmacokinetic studies

Naltrexone HCl (NAL.HCl) has been reduced at the mercury electrode in Britton–Robinson universal buffer of pH values 2–11 with a mechanism involving the quasi-reversible uptake of the first transferring electron followed by a rate-determining protonation step of its C = O double bond at position C-6. Simple, sensitive, selective and reliable linear-sweep and square-wave adsorptive cathodic stripping voltammetry methods have been described for trace quantitation of NAL.HCl in bulk form, commercial formulation and human body fluids without the necessity for sample pretreatment and/or time-consuming extraction steps prior to the analysis. Limits of quantitation of 6.0 × 10−9 M and 8.0 × 10−10 M NAL.HCl in bulk form or commercial formulation and of 9.0 × 10−9 and 1.0 × 10−9 M NAL.HCl in spiked human serum samples were achieved by the described linear and square-wave stripping voltammetry methods, respectively. Furthermore, pharmacokinetic parameters of the drug in human plasma samples of healthy volunteers following the administration of an oral single dose of 50 mg NAL.HCl (one Revia® tablet) were estimated by means of the described square-wave stripping voltammetry method without interferences from the drug's metabolites and/or endogenous human plasma constituents. The estimated pharmacokinetic parameters were favorably compared with those reported in literature.

Research highlights
► Naltrexone was reduced at Hg electrode via transfer of 2 electrons due to C = O group.
► A reversible first electron uptake followed by a protonation step was suggested.
► Reliable adsorptive stripping voltammetry methods were optimized for its analysis.
► Its assay in tablets and body fluids was carried out successfully by these methods.
► Its pharmacokinetic parameters in plasma of treated subjects were estimated.