Screening and greenness profiling of oxidative-coupling and electrophilic aromatic substitution reactions for determination of three phenolic drugs

In this study, we screened oxidative-coupling and electrophilic aromatic substitution reactions for developing simple, economic, and environment-friendly spectrophotometric methods for three widely prescribed phenolic drugs; salbutamol sulfate (SLB), terbutaline sulfate (TBT), and thymol (THY). Methods IA and IB rely on the oxidative-coupling reaction of SLB and TBT with p-phenylenediamine in the presence of an oxidizing agent in carbonate buffer while Method II depends on electrophilic aromatic substitution reaction of THY with sodium nitroprusside/hydroxylamine hydrochloride in phosphate buffer (pH 12.0). Different experimental conditions controlling the derivatization reactions were optimized and the reaction products were quantified at 552, 400, and 700 nm, for SLB, TBT, and THY, respectively. Beer's-Lambert law was obeyed over wide linearity ranges with limits of detection from 6 to 126 ppb for the target analytes. Furthermore, the developed methods were validated as per ICH guidance. In addition, profiling of the methods greenness was conducted by adopting the National Environmental Methods Index and the analytical eco-scale score approaches. The two approaches elucidated the excellent greenness of the developed methods which emphasized their applicability for quality control analysis. Thus, the developed methods were efficaciously used for the determination of the three drugs in different dosage forms with excellent accuracy, where % found ranged from 98.86%-102.77%, and no interference from additives in the formulations.