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Green, selective and accurate high-performance liquid chromatography (HPLC) chromatographic method is presented for simultaneous separation and quantitation of the co-prescribed drugs in chemotherapy omeprazole, ondansetron and deflazacort in spiked human plasma. An isocratic HPLC separation was performed on X Bridge C18 (4.6 × 250 mm) column with 5 μm particle size using mobile phase consisting of methanol: ammonium acetate buffer pH 4 adjusted by acetic acid (60: 40, v/v). The injection volume was 20μL with UV detection wavelength at 237 nm at room temperature. Flow rate of the mobile phase was adjusted to be 2.0 ml/min. Dexamethasone was used as internal standard to correct the variation during sample pretreatment. FDA guidelines were followed to validate the developed method. Successful application of the developed method was revealed by simultaneous determination of omeprazole, ondansetron and deflazacort in spiked human plasma in ranges of 1-20, 0.1-8 and 0.2-8 μg mL-1 for omeprazole, ondansetron and deflazacort, respectively. Four greenness assessment tools were used to evaluate the greenness of the developed method and the results were accepted. This method permitted the accurate simultaneous determination of the studied drugs, thus it can be used during therapeutic drug monitoring in daily clinical practice., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Piperacillin (PIP) and tazobactam (TAZ) are broad-spectrum beta-lactam antimicrobial agents, which are frequently co-prescribed in intensive care units (ICUs) worldwide. Ibuprofen (IBU) is a potent pain killer which is commonly co-prescribed with PIP and TAZ postoperatively. The combination therapy of PIP, TAZ, and IBU has been administered commonly after surgical procedures to combat aerobic and anaerobic microbes and exert anti-inflammatory and analgesic effects. This study describes, for the first time, the development of a new capillary electrophoresis (CE) method with a photodiode array detector for the simultaneous determination of PIP, TAZ, and IBU in plasma samples. The experimental factors affecting the elution of analytes were carefully optimized. The final analysis was achieved using a fused silica capillary (58 cm effective length and 75 μm ID) and a background electrolyte solution containing a methanol/borax buffer solution (15 mM and pH 9.3) in a ratio of (10 : 90 v/v) with a driving voltage of 30 kV and detection at 210 nm. The relationship between the peak area and concentration was linear from 1 to 200 μg mL -1 for both PIP and TAZ and from 3 to 200 μg mL -1 for TAZ. The method used was thoroughly validated in accordance with the validation requirements set out by the Food and Drug Administration (FDA) for bio-analytical processes. The proposed CE method was employed to conduct pharmacokinetic and bioavailability studies of the drugs in rat models. The pharmacokinetic results revealed that there is a significant impact upon prescribing this combination concurrently when compared to their single administration. To illustrate, the time required to reach their maximum concentrations ( T max ) was increased by 0.25 h for both PIP and TAZ, whereas it was increased by 0.5 for IBU. When it comes to their maximum concentration ( C max ), it was increased by 13.7%, 55.5%, and 44% for PIP, TAZ, and IBU, respectively. Furthermore, the bioavailabilities of PIP, TAZ, and IBU were significantly increased by 55.4%, 19.7%, and 35.6%, respectively. These findings require caution when these drugs are co-prescribed as there is a noticeable augmentation in their therapeutic impacts. Additionally, the greenness of the proposed method was assessed by three metric tools. In conclusion, the method is a valuable tool for further studies on drug-drug interaction in humans., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Accurate, sensitive and green HPTLC chromatographic method was proposed for simultaneous determination of metformin, glipizide and sitagliptin in the presence of metformin potential toxic impurities melamine and cyanoguanidine. The separation was completed on silica gel HPTLC F254 plates using a mixture of ethyl acetate: methanol: ammonia: formic acid (7: 2: 0.2: 0.2, by volume) as a developing system with UV scanning for the developed bands at 235 nm. The Rf values for metformin, glipizide, sitagliptin, melamine and cyanoguanidine were 0.17, 0.84, 0.67, 0.47 and 0.75, respectively. Linear responses were observed in the ranges of 0.2-3, 0.07-1.5, 1.5-5, 0.8-4 and 0.4-2 μg/band with correlation coefficients of 0.9999, 0.9998, 0.9997, 0.9996 and 0.9998 for metformin, glipizide, sitagliptin, melamine and cyanoguanidine, respectively. The proposed method was validated as per ICH criteria with respect to linearity, accuracy, precision, specificity and robustness. The validated method was successfully applied for determination of the studied drugs in Janumet® and Engilor® tablets; also, the results were statistically compared to those obtained by the reported spectrophotometric method and no significant difference was found between them. This method permitted the accurate simultaneous determination of the studied drugs, indicating its ability to be used for routine quality control assays of these drugs., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Duvelisib (DUV) is a potent anticancer drug whereas Moxifloxacin (MOX) is an antimicrobial drug with anti-proliferative potency against cancerous cells, which is empirically administered in cancer treatment. DUV and MOX combination is commonly prescribed to combat infections in patients while they are under chemotherapy treatment. This study describes, for the first time, the development of a simple and green synchronous spectrofluorimetric (SSF) method for the simultaneous estimation of DUV and MOX in plasma. DUV and MOX were quantified at 273 and 362 nm, respectively without interference between each other at Δ λ of 120 nm. The experimental variables influencing fluorescence intensities were thoroughly investigated and the optimum conditions were established. At pH 3.5, the optimum synchronous fluorescence intensity (SFI) was achieved in water solvent by using sodium acetate buffer solution. Calibration curves for DUV and MOX, correlating the SFI with the corresponding drug concentration, were linear in the range of 50-1000 ng mL -1 for both drugs, with good correlation coefficients. The method was extremely sensitive, with limits of detection of 24 and 22 ng mL -1 , and limits of quantitation of 40 and 45 ngmL -1 for DUV and MOX, respectively. The SSF method was validated according to the Food and Drug Administration (FDA) guidelines for validation of analytical procedures, and the validation parameters were acceptable. The proposed SSF method was applied to the pharmacokinetic and bioavailability studies in rats' plasma after single concurrent oral administration of both drugs. The results of the study revealed that caution should be taken with DUV dose when concurrently administered with MOX. The greenness of SSF method was assessed by three different metric tools namely Analytical Eco-scale, Green Analytical Procedure Index, and Analytical Greenness Calculator. The results confirmed that SSF method is an eco-friendly and green analytical approach. In conclusion, the proposed SSF method is a valuable tool for pharmacokinetic/bioavailability studies and therapeutic drug monitoring of simultaneously administered DUV and MOX., (© 2023 IOP Publishing Ltd.)

Background: Before it spreads to other tissues, mebendazole (MBZ), a highly effective broad-spectrum anthelmintic, is used to treat worm infestations caused by roundworms, hookworms, whipworms, threadworms (pinworms), and the gastrointestinal form of trichinosis., Objective: The development of new methods for sensitive quantification of MBZ in the presence of its degraded product is the main objective of the presented research., Method: Validated chromatographic techniques with high sensitivity (HPTLC and UHPLC) are used. The HPTLC method was adopted on silica gel HPTLC F254 plates using ethanol, ethyl acetate, and formic acid (3: 8: 0.05, by volume) as a developing system. Furthermore, the UHPLC method is a green isocratic method with a mobile phase containing methanol and 0.1% sodium lauryl sulphate (20:80, v/v)., Results: The suggested chromatographic methods are greener than the reported ones in terms of the used greenness assessment methods. To validate the developed methods, International Council on Harmonization (ICH/Q2) guidelines were followed. Successful application of the proposed methods was revealed by the simultaneous analysis of MBZ and its major degradation product, 2-amino-5-benzoylbenzimidazole (ABB). The linear ranges were 0.2-3.0, 0.1-2.0 µg/band for the HPTLC method and 2.0-50, 1.0-40 µg/mL for the UHPLC method for MEB and ABB, respectively., Conclusions: The suggested methods were used to analyze the studied drug in its commercial tablets. Both pharmacokinetic studies and quality control laboratories can make use of the suggested techniques., Highlights: Green and accurate HPTLC and UHPLC methods for the determination of MBZ and its major degradation products., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cyclizine hydrochloride (CYC) and meclozine hydrochloride (MEC) are antihistaminic drugs generally co-formulated with pyridoxine hydrochloride (PYR) to treat nausea and vomiting in pregnancy. Several analytical techniques have been applied for the determination of CYC or MEC with PYR, but determination of CYC impurity; benzhydrol (BEH) or MEC impurity; or 4-chlorobenzophenone (BEP) has not been paid attention to. Therefore, micellar UPLC method is introduced for analysis of ternary mixtures containing PYR together with both CYC and BEH (mixture I) or MEC and BEP (mixture II). Chromatographic separation was achieved using a Hypersil gold C 8 column (50 × 2.1 mm, 1.9 μm) using 0.01 M sodium dodecyl sulfate modified to pH 3.5 using phosphoric acid:acetonitrile (45:55 by volume) for mixture I and 0.1% sodium dodecyl sulfate, 0.1% sodium bicarbonate adjusted to pH 2.6 by phosphoric acid:acetonitrile (47:53 by volume) for mixture II as mobile phases. The separated peaks were detected at 230 and 245 nm for mixtures I and II, respectively. The adopted methods were validated in conformance with the International Conference on Harmonization (ICH) recommendations and were properly applied in commercial pharmaceutical formulation analysis. Comprehensive ecological comparison was achieved, confirming a higher ecological value of the presented methods compared to the earlier reported methods., (© 2022 John Wiley & Sons, Ltd.)

Remdesivir (REM) is considered the first therapeutic option approved by US Food and Drug Administration (FDA) for clinical care in case of hospitalized patients suffering in COVID-19 epidemic. In the presented multilateral comparative search, four eco friendlessness approaches -National Environmental Methods Index (NEMI), Eco-Scale Assessment (ESA), Green Analytical Procedure Index (GAPI), and Analytical Greenness metric (AGREE) are tested to assess 16 analytical chromatographic procedures reported for the analysis of the commonly used antiviral drug; Remdesivir (REM). The values of testing more than one approach when estimating the eco-friendly characters for analytical methods are illustrated in this study. On the light of the outcomes, ESA and AGREE approaches are recommended as they are easily applied and digitally presented. Furthermore, GAPI is also a reliable tool in terms of comprehensiveness for the whole analytical procedures, from sampling till the final assessment. NEMI is the easiest and fastest greenness evaluation tool; however, the information it provides is particularly of limited scope and sometimes inaccurate. To ensure greenness of chromatographic analytical methods, there must be clear planning beforehand, to reduce chemical hazards sent to environment. Additionally, it is highly recommended in method validation protocols to consider the greenness of a given analytical procedure before releasing to routine use. The LC-MS/MS analysis for the active metabolite of REM (Nuc) reported by Avataneo et al. and Du et al. proved to be the best bio-analytical methods regarding the environmental aspects depending on the GAPI and AGREE tools. However, the HPLC method for REM analysis in intravenous solution reported by Jitta et al. proved to be the greenest analytical method for determination of REM in the pharmaceutical dosage forms according to the ESA, GAPI, and AGREE tools., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

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: A simple, sensitive, and precise quadruple devisor spectrophotometric method was developed for simultaneous determination of metformin, glipizide, and sitagliptin in the 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, 0.9998, 0.9997, 0.9997, and 0.9996 for metformin, glipizide, sitagliptin, melamine, and cyanoguanidine, respectively., Conclusions: 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 the proposed method to be used for routine quality-control analysis of these drugs., Highlights: Novel application of quadruple divisor spectrophotometric technique is introduced for resolving mixtures containing five components with severely overlapping spectra. A simple and sensitive spectrophotometric method was developed for simultaneous determination of metformin, glipizide, and sitagliptin in the presence of metformin potential impurities melamine and cyanoguanidine. The validity of the proposed method was revealed as per ICH guidelines., (© The Author(s) 2021. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Noising is an undesirable phenomenon accompanying the development of widely used chemometric models such as partial least square regression (PLSR) and support vector regression (SVR)., Objective: Optimizations of these chemometric models by applying orthogonal projection to latent structures (OPLS) as a preprocessing step which is characterized by canceling noise is the purpose of this research study. Additionally, a comprehensive comparative study between the developed methods was undertaken highlighting pros and cons., Methods: OPLS was conducted with PLSR and SVR for quantitative determination of pyridoxine HCl, cyclizine HCl, and meclizine HCl in the presence of their related impurities. The training set was formed from 25 mixtures as there were five mixtures for each compound at each concentration level. Additionally, to check the validity and predictive ability of the developed chemometric models, independent test set mixtures were prepared by repeating the preparation of four mixtures of the training set plus preparation of another four independent mixtures., Results: Upon application of the OPLS processing method, an upswing of the predictive abilities of PLSR and SVR was found. The root-mean-square error of prediction of the test set was the basic benchmark for comparison., Conclusion: The major finding from the conducted research is that processing with OPLS reinforces the ability of models to anticipate the future samples., Highlights: Novel optimizations of the widely used chemometric models; application of a comparative study between the suggested methods; application of OPLS preprocessing methods; quantitative determination of pyridoxine HCl, cyclizine HCl and meclizine HCl; checking the predictive power of developed chemometric models; analysis of active ingredients in their pharmaceutical dosage forms., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The assessment of greenness of analytical protocols is of great importance now to preserve the environment. Some studies have analyzed either only the neurotransmitters, dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA), together or with other neurotransmitters and biomarkers. However, these methods have not been investigated for their greenness and were not compared with each other to find the optimum one. Therefore, this study aims to compare seven published chromatographic methods that analyzed the four neurotransmitters and their mixtures using the National Environmental Method Index, Analytical Eco-Scale Assessment (ESA), and Green Analytical Procedure Index (GAPI). As these methods cover both qualitative and quantitative aspects, they offer better transparency. Overall, GAPI showed maximum greenness throughout the analysis. Method 6 was proven to be the method of choice for analyzing the mixture, owing to its greenness, according to NEMI, ESA, and GAPI. Additionally, method 6 has a wide scope of application (13 components can be analyzed), high sensitivity (low LOQ values), and fast analysis (low retention times, especially for glutamate and GABA).

Novel, accurate, selective, and rapid high-performance liquid chromatography mass spectrometry method was developed for simultaneous analysis of amoxicillin trihydrate, dicloxacillin sodium, and their official impurity 6-aminopenicillanic acid. The chromatographic separation was carried out by applying the mixture on a C 18 column (3.5  µ m ps, 100 mm × 4.6 mm id) using acetonitrile:water (65 : 35 by volume) as a mobile phase within only 4 min. The quantitative analysis was executed using single quadrupole mass spectrometer in which electrospray ionization, selected ion monitoring, and negative mode were operated. The retention times were 1.61, 2.54, and 3.50 mins for amoxicillin, 6-aminopenicillanic acid, and dicloxacillin, respectively. The method was validated in linear ranges of 2-28  µ g mL -1 , 2-35  µ g mL -1 , and 1-10  µ g mL -1 for amoxicillin, dicloxacillin, and 6-aminopenicillanic acid, respectively. The results obtained from the suggested HPLC/MS were statistically compared with those obtained from the reported HPLC method, where no significant difference appeared respecting accuracy and precision. According to the analytical eco-scale assessment method, the proposed method was proved to be greener than the reported one, where the analysis time and the amount of the wasted effluent decreased., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Atiah H. Almalki et al.)

The introduced research presents a novel in vivo quantitative method for assay of mixtures of pregabalin and tramadol as a common combinations approved for treatment of neuropathic pain. Green analytical chemistry is a recently emerging science concerned with control of the use of chemicals harmful to the environment in various analytical methods. Consequently, a green high-performance thin layer chromatography (HPTLC) method was achieved for determination of the mixture in human plasma and urine satisfying both analytical and environmental standards. The separation was achieved on HPTLC sheets using a separating mixture of ethanol-ethyl acetate-acetone-ammonia solution (8:2:1:0.05, by volume) as a mobile phase. The sheets were dried in air then scanned at two wavelengths. For tramadol, 220 nm was chosen; however, pregabalin is an unconjugated drug, so its determination was a challenge. Hence for pregabalin, the plates were sprayed with ethanolic solution of ninhydrin (3%, w/v), to obtain a conjugated complex, which could be assessed at 550 nm. Furthermore, the developed method fulfilled the US Food and Drug Administration validation guidelines, and proved to be useful in therapeutic drug monitoring of this combination. The Eco-scale assessment protocol was implemented to determine the greenness profile of the applied method., (© 2020 John Wiley & Sons Ltd.)

Several assessment tools were recently introduced for the evaluation of the greenness of analytical methods. Each tool has advantages, disadvantages, and a unique assessment protocol. The final results obtained from each assessment tool may lead to a dissimilar conclusion about the selection of the greenest method, which makes the decision confusing as to which an assessment tool relies on. Accordingly, in this comparative case study, four greenness assessment tools-National Environmental Methods Index (NEMI), Eco-Scale Assessment (ESA), Green Analytical Procedure Index (GAPI), and Analytical GREEnness metric (AGREE)-were tested to evaluate 16 chromatographic methods described in the literature for the assessment of the commonly used antispasmodic drug Hyoscine N-butyl bromide (HNBB). The importance of applying more than one assessment tool when evaluating the greenness of analytical methods is explained in this study. Despite NEMI tool simplicity, it was the least effective in providing information about the analytical method as 14 out of 16 methods had the same NEMI pictogram. ESA and AGREE provided reliable numerical assessments that differed in their total scores whereas the total scores were out of 100 and 1 for each, respectively. AGREE has the merits over ESA with respect to automation and highlighting the weakest points in analytical techniques that need further improvements in terms of greenness. GAPI and AGREE provide fully descriptive three-colored pictograms. The main disadvantage of GAPI is complexity compared to NEMI and ESA. AGREE has the merits of simplicity and automation over GAPI. Based on the results, recommendations are made for ESA, GAPI, and AGREE tools, which provide reliable and precise results about the greenness of the method. Planning for the greenness of analytical methods should be assured before practical trials in a laboratory for reduction of chemical hazards released into the environment. Moreover, inclusion of the evaluation of greenness of analytical methods in method validation protocols is strongly recommended.

Background: Niacin (NIA) is a water-soluble vitamin and the primary treatment of pellagra. No analytical method was found to assess NIA in complex mixtures with its official impurities., Objective: Two validated, accurate, and selective chemometric models were developed to assay NIA in the presence of its four official impurities, including pyridine, a nephrotoxic and hepatotoxic substance. Additionally, the two selective chemometric models were compared by processing UV spectra in the range 220-305 nm and applying partial least squares regression (PLSR) and support vector regression (SVR) models., Method: A five levels five factors experimental design was chosen to exhibit a training set of 25 mixtures that had numerous variable percentages of tested substances. A test set consisting of 10 mixtures was designed to confirm the predictive power of the suggested models., Results: The presented results substantiate the strength of the developed multivariate calibration models to assay NIA specifically with high selectivity and accuracy (100.02 ± 1.312 and 100.04 ± 1.272 for PLSR and SVR models, respectively). The root mean square error of prediction for the validation set mixtures was applied as a main comparison tool and it was found to be 0.2016 and 0.1890 for PLSR and SVR models, respectively., Conclusions: The results of the developed models and the reported HPLC method were statistically compared, where F-values and Student's t-tests did not show significant difference in regards to accuracy and precision. The SVR model proved to be more accurate than the PLSR model, producing a high generalization capacity, while PLSR was easy to implement and fast., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Mixtures of gabapentin, tramadol and/or amitriptyline are usually recommended for treatment of neuropathic pain. Materials & methods/results: A novel GC-MS/MS method was developed to assess the studied mixture whether in pure forms or human biological fluids (plasma/urine). The chromatographic detection was performed using MS detector applying the selected ion-monitoring mode. An (Agilent, CA, USA) GC-MS with triple axis single quadrupole detector unit was used for the analysis equipped with HP-5MS (5% phenyl methyl siloxane) column. Helium was the carrier gas and positive electron impact ionization mode was applied. Conclusion: The developed method was able to assess the mixture components simultaneously within six minutes. Validation of the method was assured according to US FDA guidelines and Eco-Scale assessment.

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., (© 2020 John Wiley & Sons, Ltd.)

Background: Amiloride hydrochloride (AM) is a potassium sparing diuretic, while hydrochlorothiazide (HCZ) is the protype of thiazide diuretics. The combining of the studied drugs exhibits a synergistic effect. Moreover, HCZ prevents the potassium depletion side effect caused by AM., Objective: Two accurate and precise simultaneous chromatographic separation methods were promoted and investigated to quantify AM, HCZ, official impurities of HCZ (cholorothiazide and salamide), and the official impurities of AM (methyl 3, 5-diamino-6-chloropyrazine-2-carboxylate)., Methods: The components of the quintuple mixture were quantified by two methods. The first method was high-performance thin layer chromatography (HPTLC), where exemplary separation was achieved on silica gel HPTLC F254 plates at the stationary phase using ethyl acetate-ethanol-ammonia solution (8 + 2 + 0.2, v/v) as a developing system. Scanning of bands at 273 nm was done. The second method was a reversed-phase chromatography (RP-HPLC) method using C18 (4.6 × 100 mm) column and mobile phase comprising 0.1% phosphoric acid solution-acetonitrile (90 + 10, v/v) with UV determination at 273 nm. Adjustment of the flow rate at 1 mL/min and pH at 3.6 was performed., Results: Regarding RP-HPLC, optimum separation of the quintuple mixture was achieved within just five minutes. According to HPTLC, symmetric and sharp peaks were separated on the resulted chromatogram. Validity of the introduced methods was investigated by applying international conference on harmonization (ICH) guidelines., Conclusions: The methods were successfully applied for assays of the studied drugs in their pure and tablet forms. No significant difference was revealed through application of statistical comparison between results of the suggested methods and those of the reported method regarding both accuracy and precision., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

UV cutoff area (COA) is known to be the wavelength band where solvents used for analysis can absorb radiation and accordingly affect the absorption spectra of drugs of interest being analyzed, even if blank experiments are done to eliminate solvent interference. However, this area may show peaks of significance for some drugs, and accordingly some researchers tend to include it in analysis. This study is presenting the importance of avoiding using COA, where it may represent significant negative effect on predictive ability of some linear chemometric methods like partial least squares regression PLSR. The presented study is using previously analyzed pharmaceutical mixtures of Dapoxetine Hydrochloride (DAP) and Tadalafil (TAD) as a case study, whether in pure forms or in dosage form, where the study uses two datasets for analysis, the first aims to include COA and the second dataset avoids it, then a statistical comparison is conducted for training sets, test sets and dosage form datasets to see how far COA may interfere with analysis results. Generally, the results show significant difference in datasets for t and F statistics for analysis of dosage form sets; which reflects changes in predictive ability of used chemometric method upon inclusion of COA in absorbance datasets, and accordingly unsuitability of using COA especially for routine quality control analysis of pharmaceutical mixtures., Competing Interests: Declaration of competing interest Authors would like to declare absence of any conflicts of interest regarding this work. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

A green, accurate and specific high-performance thin-layer chromatographic (HPTLC) method was developed and validated for simultaneous quantitative determination of pyridostigmine bromide (PR), impurity B (IMP B);3-hydroxy-N-methylpyridinium bromide and impurity A (IMP A); pyridin-3-yl-dimethylcarbamate. The two pharmacopeial impurities are also its main inactive metabolites. Furthermore, IMP B is known to be its alkaline-induced degradation product. Achievable separation of the studied components required silica gel HPTLC F254 plates as a stationary phase and acetone: acetic acid (80:20, v/v) as a developing system. Scanning of the separated bands was done at 260 nm. According to green solvent selection guidelines, acetone and acetic acid are eco-friendly solvents. Validation of the developed method was insured by its acquiesce to international conference on harmonization (ICH) guidelines. The introduced method was successfully achieved for the quantitative determination of PR, IMP B and IMP A in the range of 0.4-10, 2-11 and 0.4-3.5 μg/band, respectively. Successful application of the developed method was done for determination of PR in human plasma in the range of 0.6-10 μg/band, so the proposed HPTLC can be applied in the pharmacokinetic studies. The studied drug was also analyzed in Mestinon® tablets using the developed method., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Resolution and quantitative determination of ternary mixture with severely overlapped spectra without any preliminary separation steps represents a big challenge for any analyst. Smart and novel spectrophotometric methods are continuously innovated for achieving the above mentioned target. Novel applications of ratio difference spectrophotometric technique utilizing ratio spectra and derivative ratio spectra are applied in presented work. The proposed methods included derivative ratio difference (DRD) and ratio subtraction ratio difference (RSRD) methods. Comparative study was achieved between the proposed methods and the recently developed induced ratio difference (IRD) method. The developed methods were assessed through the analysis of ternary mixtures with different ratios of Pyridostigmine bromide (PR) and its related substances; impurity a (IMP A) and impurity b (IMP B). Analysis of PR in a pharmaceutical dosage form without any interference from other inactive ingredients was also a successful application of the proposed methods. As per ICH guidelines, the proposed methods were validated ensuring their accuracy, precision and specificity. Statistical comparison between the developed methods and the reference method was done, where calculated F and t values were less than the theoretical ones in regards to accuracy and precision., (Copyright © 2018. Published by Elsevier B.V.)

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 254 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 18 (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., (© 2018 John Wiley & Sons, Ltd.)

Furosemide and spironolactone are commonly prescribed antihypertensive drugs. Canrenone is the main degradation product and main metabolite of spironolactone. Ratio subtraction and extended ratio subtraction spectrophotometric methods were previously applied for quantitation of only binary mixtures. An extension of the above mentioned methods; successive ratio subtraction, is introduced in the presented work for quantitative determination of ternary mixtures exemplified by furosemide, spironolactone and canrenone. Manipulating the ratio spectra of the ternary mixture allowed their determination at 273.6nm, 285nm and 240nm and in the concentration ranges of (2-16μgmL -1 ), (4-32μgmL -1 ) and (1-18μgmL -1 ) for furosemide, spironolactone and canrenone, respectively. Method specificity was ensured by the application to laboratory prepared mixtures. The introduced method was ensured to be accurate and precise. Validation of the developed method was done with respect to ICH guidelines and its validity was further ensured by the application to the pharmaceutical formulation. Statistical comparison between the obtained results and those obtained from the reported HPLC method was achieved concerning student's t-test and F ratio test where no significant difference was observed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Hepatic artery aneurysms are uncommon visceral aneurysms that are usually found incidentally on imaging. We present a case of large common hepatic aneurysm presenting with life-threatening hematemesis due to duodenal erosion, in a 66-year-old man, treated by embolization with Onyx and coils while preserving hepatic perfusion.

Spontaneous femoral artery pseudoaneurysm is a rare disease and reported cases are very rare. Most of them are related to an underlying pathology of either atherosclerotic disease or connective tissue disease. We present a healthy, 29-year-old man with 2-month history of a painful pulsating mass at the level of the lower right thigh with no previous history of trauma, surgery, or puncture of the femoral artery. An angiogram revealed a right superficial femoral artery pseudoaneurysm. It was treated surgically by resection of the aneurysm and reconstruction with an interpositional saphenous vein graft. We report this case because of the rarity of this condition in a young patient with no underlying pathology., (Copyright © 2013 Elsevier Inc. All rights reserved.)