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.

Currently, analytical scientists are paying special attention to reducing reliance on hazardous chemicals in various analytical methods. By embracing this concept, we developed an eco‐friendly high‐performancethin‐layer chromatography (HPTLC) method as an alternative for the conventional HPLC method for the determination of an essential human micronutrient, niacin (NIA), which is used improve the lipid profile of patients. Furthermore, the proposed HPTLC method is capable of determining the structurally related impurities of NIA such as pyridine‐2,5‐dicarboxylic acid, isonicotinic acid, pyridine, and 5‐ethyl‐2‐methylpyridine, which exhibit nephrotoxic and hepatotoxic effects. The separation of this challenging mixture was achieved on HPTLC sheets using a mixture of ethyl acetate/ethanol/ammonia solution (6:4:0.05, v/v/v), and then the dried plates were scanned at 254 nm. The analytical eco‐scale assessment protocol was used to assess the greenness profile of the presented method and compare it with the reported HPLC method. The suggested method was found to be greener with regard to the consumption of solvents and the yielding of waste. The results suggest that the described method can be safely implemented for the routine analysis of NIA pharmaceutical dosage without the interference of potential impurities in quality control laboratories.

Novel manipulations of the well-established multivariate calibration models namely; partial least square regression (PLSR) and support vector regression (SVR) are introduced in the presented comparative study. Two preprocessing methods comprising first derivatization and orthogonal projection to latent structures (OPLS) are implemented prior to modeling with PLSR and SVR. Quantitative determination of pyridostigmine bromide (PR) in existence of its two associated substances; impurity a (IMP A) and impurity b (IMP B); was utilized as a case study for achieving comparison. A series consisting of 16 mixtures with numerous percentages of the studied compounds was applied for implementation of a 3 factor 4 level experimental design. Additionally, a series consisting of 9 mixtures was employed in an independent test to verify the predictive power of the suggested models. Significant improvement of predictive abilities of the two studied chemometric models was attained via implementation of OPLS processing method. The root mean square error of prediction RMSEP for the test set mixtures was employed as a key comparison tool. About PLSR model, RMSEP was found 0.5283 without preprocessing method, 1.1750 when first derivative data was used and 0.2890 when OPLS preprocessing method was applied. With regard to SVR model, RMSEP was found 0.2173 without preprocessing method, 0.3516 when first derivative data was used and 0.1819 when OPLS preprocessing method was applied.

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Background The presented quadruple divisor spectrophotometric method was able to resolve and analyze a complex quintuple drug matrix with severe overlapped spectra without previous separation or extraction steps or need of complicated apparatus like chromatographic methods and had the advantage of being green as the solvent used was water. Method Simple, sensitive and precise quadruple devisor spectrophotometric method was developed for simultaneous determination of metformin, glipizide, and sitagliptin in presence of metformin potential impurities melamine and cyanoguanidine. The proposed method was applied for analysis of metformin, glipizide, and sitagliptin in pure form and pharmaceutical formulation (tablets). The developed method was validated and met the requirements for ICH guidelines with respect to linearity, accuracy, precision, specificity and robustness. Results A linear response was observed in the range of 2-27, 2-20, 1-20, 0.5-10, and 1-10 μg/mL for metformin, glipizide, sitagliptin, melamine and cyanoguanidine, respectively with a correlation coefficient of 0.9996 and 0.9998, 0.9997, 0.9997 and 0.9996 for metformin, glipizide, sitagliptin, melamine and cyanoguanidine, respectively. Conclusion The validated method was successfully applied for determination of the studied drugs in Janumet® and Engilor® tablets; moreover the results were statistically compared to those obtained by the reported RP-HPLC method and no significant difference was found between them; indicating the ability of proposed method to be used for routine quality control analysis of these drugs.