Comparative Liquid Chromatographic Study for Concurrent Determination of Canagliflozin and Metformin in Combined Tablets

New HPLC-UV method (method A), for simultaneous determination of metformin (MET) and canagliflozin (CANA), was developed and compared to another novel UPLC-UV method (method B) in their tablet combination. Concerning method A, isocratic separation was done by C18 column (100 mm × 2.1 mm, 3 μm) using methanol and 0.03 M phosphate buffer (75:25, v/v) at pH 3.2 as a mobile phase. Meanwhile, chromatographic separation in method B was achieved via Hypersil® gold (50 mm × 2.1 mm, 1.9 μm). Mobile phase was methanol and 0.03 M phosphate buffer at ratio of 80:20  v/v. In both, detection was done at wavelength of 240 nm. Method A showed satisfactory linearity results over 1–50 μg·mL−1 and 0.5–100 μg·mL−1, while method B linearity was at 0.1–50 μg·mL−1 and 0.25–100 μg·mL−1 for CANA and MET, respectively. In terms of accuracy and precision, method A accuracy was 99.81±0.73 and 99.37±0.54, while method B gave accuracy of 99.47±1.03 and 99.73±0.89 for CANA and MET, respectively. For precision, the % RSD was found to be less than 2% for three concentrations analyzed three times. The two methods are convenient for quality laboratories, yet the UPLC method offered the advantage of shorter run times and higher sensitivity

Application of multiple reaction monitoring for quantitation of sweeteners in food products

A coupled UPLC-MS/MS method has been developed and validated for the simultaneous quantitation of food sweeteners stevioside (STV) and aspartame (ASP). Good chromato-graphic separation was achieved on a Hypersil gold 50×2.1 mm (1.9 μm) column, using a gradient flow of 10 mM ammonium acetate, pH = 2.9 adjusted with formic acid, and 10 mM ammonium acetate in acetonitrile:water (95:5, v:v) as the mobile phase. The eluate was introduced to ESI-Mass spectrometer and scanned using multiple reaction monitoring (MRM). The method was robust, reproducible and easy to use and was validated according to ICH guidelines for the accuracy and precision giving acceptable ranges. The utilization of multiple reaction monitoring improved the selectivity of detection. Method was linear in the ranges of 2-250 ng/mL for STV and ASP. Application of this method on laboratory mixtures of the selected sweeteners was successful. The using of mass spectrometry make the method selective and measurement did not affect the presence of impurities, additive and other ingredients of detection due to the simplicity and sensitivity of this method allows the utilization of method in quality control of STV and ASP

Utilization of UPLC-tandem mass spectrometry for quantitation of colouring matters in dietary formulation

A simple and sensitive ultra-performance liquid chromatography with Tandem Mass Spectrometric detection (UPLC-MS/MS) method was developed and validated for the simultaneous quantitation of two food colouring matters, Curcumin (CUR) and Riboflavin (RIB). Chromatographic separation was done on Hypersil gold 50×2.1 mm (1.9 μm) column, with gradient programing of mobile phase starting with aqueous 0.1% formic acid and increasing the percentage of 0.1% formic acid in acetonitrile. The utilization of multiple reaction monitoring (MRM) improved the selectivity of detection and decreased the matrix effect.  The method was linear in the range of 5-500 ng/mL for CUR and RIB. Intra- and inter-day reproducibility were within the accepted criteria. The method was successfully applied for the determination the laboratory prepared mixtures of the two selected colouring matters. The use of mass spectrometry enhanced the selectivity and sensitivity of detection which allows the robust use of the method in routine quality control tests of the two colouring matters (CUR and RIB)

3-Ethoxymethyl-1,4-dihydroquinolin-4-one

In the title molecule, C12H13NO2, the dihydroquinolinone fused-ring system is nearly planar [maximum deviation = 0.012 (3) Å], and the mean plane passing through the extended ethoxymethyl substituent is aligned at 86.9 (2)° with respect to the fused-ring system. In the crystal, adjacent molecules are linked by an N—H...Ocarbonyl hydrogen bond to generate a chain running along the b-axis direction

Different Spectrophotometric Methods for Simultaneous Determination of Trelagliptin and Its Acid Degradation Product

New spectrophotometric and chemometric methods were carried out for the simultaneous assay of trelagliptin (TRG) and its acid degradation product (TAD) and applied successfully as a stability indicating assay to recently approved Zafatek® tablets. TAD was monitored using TLC to ensure complete degradation. Furthermore, HPLC was used to confirm dealing with one major acid degradation product. The proposed methods were developed by manipulating zero-order, first-derivative, and ratio spectra of TRG and TAD using simultaneous equation, first-derivative, and mean-centering methods, respectively. Using Spectra Manager II and Minitab v.14 software, the absorbance at 274 nm–260.4 nm, amplitudes at 260.4 nm–274.0 nm, and mean-centered values at 287.6 nm–257.2 nm were measured against methanol as a blank for TRG and TAD, respectively. Linearity and the other validation parameters were acceptable at concentration ranges of 5–50 μg/mL and 2.5–25 μg/mL for TRG and TAD, respectively. Using one-way analysis of variance (ANOVA), the optimized methods were compared and proved to be accurate for the simultaneous assay of TRG and TAD

Synthesis and crystal structures of (E)-N′-(4-chloro-3-nitrobenzylidene)acetohydrazide and (E)-2-(4-chlorobenzylidene)-1-(quinolin-8-yl)hydrazine

The syntheses of two benzylidenehydrazine derivatives, namely, (E)-N′-(4-chloro-3-nitrobenzylidene)acetohydrazide, C9H8ClN3O3, and (E)-2-(4-chlorobenzylidene)-1-(quinolin-8-yl)hydrazine, C16H12ClN3, are reported. The molecules have been characterized using IR, 1H NMR, 13C NMR and mass spectroscopic and elemental analysis techniques, and their structures have been determined by single-crystal X-ray diffraction

Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-ones and 1,3,4-Oxadiazole-2-thiones

A series of fenamate pyridyl or quinolinyl analogues of 1,3,4-oxadiazol-2-ones 5a-d and 6a-r, and 1,3,4-oxadiazole-2-thiones 5e-g and 6s-v, respectively, have been synthesized and evaluated for their analgesic (hot-plate) , antiinflammatory (carrageenin induced rat\u27s paw edema) and ulcerogenic effects as well as plasma prostaglandin E2 (PGE2) level. The highest analgesic activity was achieved with compound 5a (0.5 ,0.6 ,0.7 mrnolkg b.wt.) in respect with mefenamic acid (0.4 mmollkg b.wt.). Compounds 6h, 6l and 5g showed 93, 88 and 84% inhibition, respectively on the carrageenan-induced rat\u27s paw edema at dose level of 0.1rnrnol/kg b.wt, compared with 58% inhibition of mefenamic acid (0.2mmoll kg b.wt.). Moreover, the highest inhibitory activity on plasma PGE2 level was displayed also with 6h, 6l and 5g (71, 70,68.5% respectively, 0.lmmolkg b.wt.) compared with indomethacin (60%, 0.01 mmolkg b.wt.) as a reference drug. In addition 6i, 6k, 6p, 6r, 6t and 6v were devoid of any ulcerogenicity

QSAR-based rational discovery of novel substituted-4′-iminospiro[indoline-3,3′-[1,2,5]thiadiazolidinyl]-2-one 1′,1′-dioxide with potent in vitro anticancer activity

Abstract Recent studies have suggested that aldose reductase inhibition preferentially inhibits the growth of cancer cells. However, the investigations of this issue are not many. Novel nine substituted- 4′-iminospiro[indoline-3,3′-[1,2,5] thiadiazolidinyl]-2-one 1′,1′-dioxide derivatives were designed by both isosteric replacement of the imidazolidine-2,5-dione moiety in spirohydantoin scaffold and conformational rigidification approaches. A QSAR with high predictive power (r2 = 0.99) was created from a series of potent aldose reductase inhibitors and was used to predict the activity of our new compounds. Compound 5 showed the best docking score (− 33.24 kcal/mol) with the least RMSD value (< 1.5) obtained by molecular dynamic simulations over 20 ns. All compounds showed promising anticancer activities especially compound 5 that achieved the highest inhibitory activities with IC50; 0.013, 0.031, 0.064, and 0.048 mmol/L against breast, colon, prostate, and lung cell lines respectively. The discovery of this lead compound confirmed the rational design. Further investigations may be required for optimization of this compound