Thyrotoxicosis antidote assay along with concurrent medication; chromatographic and environmental issues

Abstract

A thionamide medication, Methimazole (MTZ), is a crucial antidote of thyroid hormone in cases of toxic nodular goiter or thyrotoxicosis by decreasing thyroid hormone synthesis. Propranolol (PRP), a beta blocker, is commonly co-administered with MTZ for controlling tachycardia associated with hyperthyroidism. Quantitative determination and tracing of MTZ in plasma in the presence of its co-administered medication, like PRP, is of paramount importance due to the reported toxic manifestations related to MTZ long-term administration that include agranulocytosis, hepatitis, arthritis, and skin rashes. An environmentally benign FDA-validated TLC densitometric approach was established for the first time for simultaneous and quantitative analysis of MTZ and PRP in pure form and spiked human plasma. The work is considered a mimetic study for their co-administration. Successful resolution between them was achieved on Merck^® silica gel plates using a mixture of ethyl acetate: acetone: 33% NH₃ solution in a ratio of (9: 1: 0.05, by volume) as a developing phase and UV scanning at 254 nm. Adding hydrocortisone acetate (HCA) as an internal standard eliminated the matrix effect variation. Reasonable resolution of the developed peaks was attained, with R_f values of 0.07, 0.19, 0.67, and 0.81 for plasma, PRP, MTZ, and HCA, respectively. Four greenness and viability rating approaches were applied to check and measure the greenness aspects of the suggested method toward the eco-system, and the outcomes were convenient and satisfactory. Also, the verification domains were tested using US-FDA bio-analytical specifications where reliable and acceptable outcomes were obtained with satisfied % recoveries for the quality control samples ranging from (100.39–104.44%) and (96.01–100.72%) for MTZ and PRP, respectively, with low RSD values indicating good accuracy and precision of the proposed method.