Selective Monitoring of Anti-Cancer Drug in Real Sample Matrix Employing Nanomaterial Based Electrochemical Biosensor

Abstract

Alkaloids are the roots of the pharmaceutical industry which has emerged in the forms of analgesic, anti-arrhythmic, muscle relaxant, anti-hypertensive, anti-cancer drugs and other variants. Alkaloids portray a critical role in the defense systems against pathogens and animals. The significance of alkaloids is not restrained to biological control but also have pharmacological, veterinary and medical importance. There are numerous alkaloids which are obtained from plants resulting in serious illness, injury or even death. Strychnine and brucine are structurally associated with monoterpenoid indole alkaloids and primarily source is the seeds of Strychnos nux-vomica, a traditional medicine which has been used in clinical practice. When such alkaloids like brucine are consumed, it incites the central nervous system and the sensory organs become more sensitive. Hence, at low doses is often used to treat nervous diseases, arthritic and traumatic pains. Brucine, 2, 3- dimethoxystrychnidin- 10- one is a natural alkaloid which has shown to possess array of biological activities. Recent investigations have shown cytotoxic, anti-tumor, antiangiogenic and anti-proliferative effects of brucine on multiple myeloma cell lines and human LoVo cell line. Brucine has also been reported for thermo-chemotherapy of tumor along with thermosensitive liposomes in combination with local hyperthermia. Hepatocellular carcinoma is mainly influenced by metastasis and brucine was found to impede its migration in vitro and metastasis in vivo extraordinarily. Although brucine exhibits impressive preclinical results for the pharmacological activities, the principal complication in its clinical application still exists due to acute toxicity in central nervous system. There is a thin line of safety between a therapeutic and a toxic dose thereby indicating that an improved method for the determination of trace levels of brucine in biological fluids is required for toxicological research, clinical study and forensic analysis. Consequently, the development of a simple, inexpensive, sensitive and accurate analytical method for determination of brucine is of considerable importance. Herein, we report the selective and sensitive determination of brucine on single walled carbon nanotubes and nafion composite, modified on glassy carbon electrode employing square wave voltammetry for the first time. Voltammetric studies indicated the oxidation of brucine at the electrode surface through a two electron and two proton irreversible step and fundamentally controlled by adsorption. A good linear range from 1 nM to 8 µM with a high sensitivity of 340.8 µA µM-1 and limit of detection corresponding to 0.11 nM was achieved. The interference of coexisting metabolites on the current response of brucine has been assessed. Furthermore, the proposed method was successfully applied to the real samples such as human serum and urine for the determination of brucine in order to elucidate the performance in human physiology. The investigation of brucine concentration has been satisfactorily carried out in S. nux vomica seeds which are the natural source of brucine. The results illustrate that this method is facile, highly selective and expeditious; thus, providing a powerful tool for the monitoring of brucine. Enhancements in the quantification of brucine will commence its engagement for the metastasis of hepatocellular carcinoma for therapeutic use.