Development of an eco-friendly capillary electrophoresis method for the simultaneous determination of piperacillin, tazobactam and ibuprofen in plasma samples: application to a pharmacokinetic study in rats

Abstract

Piperacillin (PIP) and tazobactam (TAZ) are broad-spectrum beta-lactam antimicrobial agents, which are frequently co-prescribed in intensive care units (ICUs) worldwide. Ibuprofen (IBU) is a potent pain killer which is commonly co-prescribed with PIP and TAZ postoperatively. The combination therapy of PIP, TAZ, and IBU has been administered commonly after surgical procedures to combat aerobic and anaerobic microbes and exert anti-inflammatory and analgesic effects. This study describes, for the first time, the development of a new capillary electrophoresis (CE) method with a photodiode array detector for the simultaneous determination of PIP, TAZ, and IBU in plasma samples. The experimental factors affecting the elution of analytes were carefully optimized. The final analysis was achieved using a fused silica capillary (58 cm effective length and 75 μm ID) and a background electrolyte solution containing a methanol/borax buffer solution (15 mM and pH 9.3) in a ratio of (10 : 90 v/v) with a driving voltage of 30 kV and detection at 210 nm. The relationship between the peak area and concentration was linear from 1 to 200 μg mL⁻¹ for both PIP and TAZ and from 3 to 200 μg mL⁻¹ for TAZ. The method used was thoroughly validated in accordance with the validation requirements set out by the Food and Drug Administration (FDA) for bio-analytical processes. The proposed CE method was employed to conduct pharmacokinetic and bioavailability studies of the drugs in rat models. The pharmacokinetic results revealed that there is a significant impact upon prescribing this combination concurrently when compared to their single administration. To illustrate, the time required to reach their maximum concentrations (T_max) was increased by 0.25 h for both PIP and TAZ, whereas it was increased by 0.5 for IBU. When it comes to their maximum concentration (C_max), it was increased by 13.7%, 55.5%, and 44% for PIP, TAZ, and IBU, respectively. Furthermore, the bioavailabilities of PIP, TAZ, and IBU were significantly increased by 55.4%, 19.7%, and 35.6%, respectively. These findings require caution when these drugs are co-prescribed as there is a noticeable augmentation in their therapeutic impacts. Additionally, the greenness of the proposed method was assessed by three metric tools. In conclusion, the method is a valuable tool for further studies on drug–drug interaction in humans.