Canagliflozin is a newly approved drug for type II diabetes mellitus. A full stability study of canagliflozin was performed following international conference on harmonization strategies. The drug was stable against all conditions except oxidation where only one degradation product was separated and structurally elucidated using mass spectrometry and infrared spectroscopy. A green high-performance thin-layer chromatographic densitometric determination was developed and validated for the accurate quantification of canagliflozin and its main oxidative degradation product. Separation was performed on high-performance aluminum plates precoated with silica gel using acetone/ethanol (80:20, v/v) as a developing system and scanning at 290 nm. Retardation factor values were 0.64 and 0.81 and linearity ranges were 0.4-3.6 and 0.2-3.2 μg/band for the drug and the degradation product, respectively. It was a matter of interest to use green solvents with no harmful effects on the environment. The comparison between the proposed and the reported high-performance liquid chromatography method regarding greenness profile showed that the proposed method was greener and so could be used as an alternative method to the reported one with no environmental harm. Method validity was tested as per international conference on harmonization and method utility was verified by application to Invokana® tablets.

Two selective and accurate chromatographic methods are presented for simultaneous quantitation of spironolactone (SP) and furosemide (FR) and canrenone (CN), the main degradation product and the main active metabolite of SP. Method A was HPTLC, where separation was completed on silica gel HPTLC F plates using ethyl acetate-triethylamine-acetic acid (9:0.7:0.5, by volume) as a developing system and UV detection at 254 nm. Method B was a green isocratic RP-HPLC utilizing a C (4.6 × 100 mm) column, the mobile phase consisting of ethanol-deionized water (45: 55, v/v) and UV estimation at 254 nm. Adjustment of flow rate at 1 mL/min and pH at 3.5 with glacial acetic acid was done. Regarding the greenness profile, the proposed RP-HPLC method is greener than the reported one. ICH guidelines were followed to validate the developed methods. Successful applications of the developed methods were revealed by simultaneous determination of FR, SP and CN in pure forms and plasma samples in the ranges of 0.2-2, 0.05-2.6 and 0.05-2 μg/band for method A and 5-60, 2-60 and 2-60 μg/mL for method B for FR, SP and CN, respectively.

Recently, concepts of sustainable developments, like considering the environmental effect of chemicals used and the amount of hazardous wastes produced, has gained much interest. In this work, a recently approved treatment for type II diabetes mellitus, canagliflozin, was quantified along with its degradation product by two eco-friendly methods. The first was a specific green HPLC method using a C 18 column as a stationary phase and a mobile phase consisting of methanol-water (98:2, v/v) pumped at a flow rate of 1 mL/min with UV detection at 225 nm, and using ibuprofen as an internal standard. The second method was a partial least square chemometric method with the wavelength range 220-320 nm and the data was autoscaled as a preprocessing step for determination of canagliflozin and its degradation product.The greenness profile of the developed methods was studied and compared with the reported methods. The proposed methods were suitable alternatives for the environmentally harmful reported methods for quality control analyses of canagliflozincontaining samples, analysis of pharmaceutical formulations and sensitive tracing of its possible degradation product. The methods were validated as per International Conference on Harmonization guidelines and statistically compared with the reported HPLC method.

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