Manipulation and Processing of Spectral Signals for the Assay of the Newly Authorized Mixture of Bupivacaine/Meloxicam Using Fully Green Solvents and a Comparative Green Evaluation Supporting the Greenness and Sustainability of the Developed Smart Spectrophotometric Methods.

Background: The bupivacaine (BVC)/meloxicam (MLX) combination is the first extended-release dual-acting local anesthetic (DALA) that provides 72 h of postoperative pain relief. It reduces opioid use after surgery and manages pain better than BVC alone over 72 h, and overcomes surgical site inflammation with a new synergistic mode of action that combines BVC with a low dosage of MLX.

Objective: In today's pharmaceutical research, we take great care to only use non-toxic solvents that pose no threat to either humans or the environment. This work determines BVC and MLX simultaneously, utilizing water and 0.1 M HCl in water as solvents. Moreover, the eco-friendliness of the specified solvents and the whole method development steps was evaluated based on how user-friendly they were using four standard methodologies.

Methods: The developed spectrophotometric methods depended on either zero-order, derivative, or ratio spectra that only required simple mathematical handling. The current techniques include dual wavelength (DW), Fourier self-deconvolution (FSD), first derivative (D1), ratio difference (RD), and first ratio derivative (DD1).

Results: Linearity was confirmed over a concentration range of 50-700 μg/mL for BVC and 1-10 μg/mL for MLX. For BVC and MLX, the LOQs were 26.85-41.33 μg/mL and 0.21-0.95 μg/mL, while the LODs were 8.86-13.64 μg/mL and 0.06-0.31 μg/mL, respectively. For the full validation of the proposed methods, ICH (international conference on harmonization) criteria were followed.

Conclusion: Current methods have the advantage of sticking to the basis of zero-order, derivative, or ratio spectra and needing just the barest minimum of data processing: no complex software, lengthy stages, or transformations are needed.

Highlights: No spectrophotometric methods have been published for the simultaneous analysis of BVC and MLX. As a result, the newly developed spectrophotometric approaches have great relevance and originality in the field of pharmaceutical analysis.