Environmentally benign first derivative synchronous spectrofluorimetry for the analysis of two binary mixtures containing duloxetine with avanafil or tadalafil in spiked plasma samples.

Antidepressants can cause sexual dysfunction side effects, necessitating the co-administration of phosphodiesterase type 5 inhibitors. The simultaneous determination of these drugs in biological fluids is critical for therapeutic drug monitoring. For the first time, two binary mixtures containing duloxetine with either avanafil or tadalafil were estimated utilizing simple green spectrofluorimetric methods without the need for a previous separation step. The study was based on first derivative synchronous spectrofluorimetry in ethanol using a change in wavelength difference (∆λ) of 20 and 25 nm for the first and second combinations, respectively. Duloxetine and avanafil were estimated at 297.7 and 331 nm in their binary mixture, while duloxetine and tadalafil were determined at 290.3 and 297.7 nm, respectively. The linearity was achieved over the ranges of 0.1-1.5 µg mL-1 for both duloxetine and avanafil and 0.01-0.40 µg mL-1 for tadalafil, with limits of detection of 0.013, 0.022, and 0.004 µg mL-1 for duloxetine, avanafil, and tadalafil, respectively. Successful application of the developed approaches was accomplished for the estimation of the two mixtures in dosage forms as well as human plasma with excellent percentage recoveries (96-103.75% in plasma), which supports their suitability for use in quality control laboratories and pharmacokinetic studies. Moreover, the adopted approaches' greenness was evidenced by applying three tools.

Utility of synchronous fluorimetry for the concurrent quantitation of metoprolol and ivabradine.

Metoprolol combined with ivabradine have been determined up to nanogram level simultaneously relied on the synchronous fluorescence spectra. First derivative amplitudes of the synchronous spectrofluorimetric spectra are recorded at Δλ = 40 nm using ethanol as diluting solvent. Metoprolol can be measured at 286 nm which is the zero-crossing point of ivabradine, and the later can be measured at 296 nm. The calibration plots were found to be linear over the ranges of concentrations: 100.0-1000.0 ng/mL and 10.0-200.0 ng/mL for metoprolol and ivabradine, respectively. Validation of the procedure was performed using the International Council of Harmonization guidelines. Values of LODs were found to be 28.89, 2.80 ng/mL and LOQs were 87.56, 8.49 ng/mL for metoprolol and ivabradine, respectively. As the two drugs are co-administered safely and effectively to reduce heart rate, angina attacks, the current methodology is utilized for the concurrent analysis of them in their single ingredient pharmaceutical preparations, synthetic mixtures, and biological fluids. The designed method, being cost-effective and simple procedure, is the first method for metoprolol and ivabradine simultaneous analysis. The results agreed statistically with the comparison methods.