title: A comparative study of ICH validated novel spectrophotometric techniques for resolving completely overlapping spectra of quaternary mixtures.
abstract: A pharmaceutically marketed mixture of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine co-formulated as a promising therapy for erectile dysfunction. Simultaneous determination of the aforementioned pharmaceutical formulation without prior separation steps was applied using mean centering of ratio spectra and triple divisor spectrophotometric methods. Mean centering of ratio spectra method depended on using the mean centered ratio spectra in three successive steps which eliminated the derivative steps and so the signal to noise ratio was improved. The absorption spectra of the prepared solutions were measured in the wavelength range of 215-300 nm in the concentration ranges of 1-15, 3-15, 1-20, and 3-15 μg mL(-1) for Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. The amplitudes of the mean centered third ratio spectra were measured at 250 nm and 268 nm for Yohimbine and Alpha-tocopheryl acetate, respectively and at peak to peak 272-273 and 262-263 nm for Niacin and Caffeine, respectively. In triple divisor method each drug in the quaternary mixture was determined by dividing the spectrum of the quaternary mixture by a standard spectrum of a mixture containing equal concentrations of the other three drugs. First derivative of these ratio spectra was obtained where determination could be achieved without any interference from the other three drugs. Amplitudes of 1-15, 3-15, 1-15, and 3-15 μg mL(-1) were used for selective determination of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. Laboratory prepared mixtures were analyzed by the developed novel methods to investigate their selectivity also, Super Act® capsules were successfully analyzed to ensure absence of interference from additives. The developed methods were validated according to the ICH guidelines. The proposed methods were statistically compared with each other and with the reported methods; using student t-test, F-test, and one way ANOVA, where no significant difference was found with respect to accuracy and precision.
authors.affiliation: Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Al shaheed Shehata Ahmed Hegazy st., 62514 Beni-Suef, Egypt. Electronic address: nour74ali@yahoo.com.
authors.forename: Nouruddin W
authors.initials: NW
authors.lastname: Ali
authors.affiliation: Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Al shaheed Shehata Ahmed Hegazy st., 62514 Beni-Suef, Egypt.
authors.forename: Nada S
authors.initials: NS
authors.lastname: Abdelwahab
authors.affiliation: Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini st., 11562 Cairo, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Abdelkawy
authors.affiliation: Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Al shaheed Shehata Ahmed Hegazy st., 62514 Beni-Suef, Egypt.
authors.forename: Aml A
authors.initials: AA
authors.lastname: Emam
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000032:analysis; D000704:Analysis of Variance; D000975:Antioxidants / Q000032:analysis; D002110:Caffeine / Q000032:analysis*; D000697:Central Nervous System Stimulants / Q000032:analysis; D004338:Drug Combinations; D009525:Niacin / Q000032:analysis*; D013053:Spectrophotometry / Q000379:methods*; D014665:Vasodilator Agents / Q000032:analysis; D015016:Yohimbine / Q000032:analysis*; D024502:alpha-Tocopherol / Q000032:analysis*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000975:Antioxidants; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D014665:Vasodilator Agents; D009525:Niacin; D015016:Yohimbine; D002110:Caffeine; D024502:alpha-Tocopherol
keywords: Alpha-tocopheryl acetate; Caffeine; Mean centering of ratio spectra; Niacin; Triple divisor; Yohimbine