Abstract
The purpose of this study was to develop and validate a high-performance liquid chromatographic–tandem mass spectrometric (LC–MS/MS) method for analysis of the bromantane in human plasma. The analyte and Internal Standard (IS), selenox, were extracted from human plasma by solid-phase extraction and separated on a Zorbax SB-C18 column using methanol–0.2% formic acid as mobile phase. Detection was performed using an atmospheric pressure chemical ionization source and mass spectrometric positive Multi-Reaction-Monitoring-Mode (+MRM) at an ion voltage of +2000 V. The assay was linear over the concentration range 1–500 ng/mL with the Lowest Limit of Quantification (LLOQ) of 1 ng/mL. The method also afforded satisfactory results in terms of the sensitivity, specificity, precision (intra- and inter-day, CV<10%), accuracy, recovery as well as the stability of the analyte under various conditions. The method can be applied to pharmacokinetic and toxicological studies.
Highlights
Bromantane, N-(4-bromophenyl) adamantan-2-amine, is a drug with anxiolytic and immunostimulatory actions and elements of actoprotective activity [1,2,3]
The therapeutic action of Bromantane in patients with asthenic and anxiety-asthenic disorders is exhibited from first day of application, which is expressed by a marked reduction of asthenic symptoms, signs of emotional tension, and somatoautonomic manifestations; the drug works by restoring performance and enhancing the endurance of the body
Electrospray ionization is often used as an LC-MS interface, atmospheric pressure chemical ionization (APCI), another type of atmospheric pressure ionization, is more applicable to low polarity compounds [15]
Summary
Bromantane, N-(4-bromophenyl) adamantan-2-amine, is a drug with anxiolytic and immunostimulatory actions and elements of actoprotective activity [1,2,3]. The use of the drug, in contrast to the action of a typical psycho stimulant, is not associated with the phenomenon of hyper stimulation and causes no consequences such as functional exhaustion of the body [4]. These properties of drug stipulated its using as a doping agent [5]. Its mechanism of action is associated with the release of reinforcing dopamine from the presynaptic terminal [7], blockade of its reuptake, and enhancement of biosynthesis and induced tyrosine hydroxylase gene expression, as well as with a modulatory effect on the Benzodiazepine-GABA-receptor-chloride ion channel complex, upregulating the stress-induced decrease of benzodiazepine reception. Bromantane has low toxicity (LD50 in rats is higher than 10000 mg/kg, exceeding the effective dose by 100 times)
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