Therapeutic drug monitoring of two co-administered drugs through development of two ecological chromatographic methods: Invivo application

Abstract

Surgical site infections (SSI) and pain are the most common postoperative serious complications that increase hospitalization period, treatment cost, and rate of morbidity. Tinidazole (TNZ) and Ibuprofen (IBU) are among the most widely used postoperative and inpatient drugs. The former is used in prophylaxis and treatment of infections, whereas, the later provides long-lasting analgesia and reduces opioid consumption. Therapeutic drug monitoring (TDM) is required for TNZ to decrease the generation of antimicrobial resistance, maximize its efficacy and minimize its toxicity. Additionally, TDM of IBU may be required due to its substantial variability in disposition and clearance. No available method for the simultaneous determination of TNZ and IBU. Hence, the current work aimed to develop two green liquid chromatographic methods for TDM of the mentioned drugs. The first was a TLC-densitometric method using a mobile phase of ethylacetate: ethanol: 33% ammonia solution in the ratio of (7.5: 2.5: 0.05, by volume) using cyclizine as internal standard. The second method was an HPLC method, using methanol: 0.05 M K2HPO4 buffer pH 8 and sulphasalazine as an internal standard. The optimized methods demonstrated adequate sensitivity for the determination of the mentioned drugs as low as 0.98–8.4% of their reported Cmax. Thus, the methods were successfully applied for in-vivo TDM of the mentioned drugs. Bioanalytical validation parameters met the acceptance criteria of US FDA guidelines. NEMI, AMVI and eco scale metrics were applied for qualitative and quantitative assessment of the methods’ greenness. Being green, time and money-saving, the developed methods can be used for TDM of these inpatient drugs in clinical studies.