Quality-by-design ecofriendly potentiometric sensor for rapid monitoring of hydroxychloroquine purity in the presence of toxic impurities.

Hydroxychloroquine (HCQ) is prescribed to treat malaria and certain autoimmune diseases. Recent studies questioned its efficiency in relieving COVID-19 symptoms and improving clinical outcomes. This work presents a quality-by-design approach to develop, optimize, and validate a potentiometric sensor for the selective analysis of HCQ in the presence of its toxic impurities (key starting materials), namely 4,7-Dichloroquinoline (DCQ) and hydroxynovaldiamine (HND). The study employed a custom experimental design of 16 sensors with different ion exchangers, plasticizers, and ionophores. We observed the Nernstian slopes, correlation coefficients, quantification limit, response time, and selectivity coefficient for DCQ and HND. The computer software constructed a prediction model for each response. The predicted responses strongly correlate to the experimental ones, indicating model fitness. The optimized sensor achieved 93.8% desirability. It proved a slope of 30.57 mV/decade, a correlation coefficient of 0.9931, a quantification limit of 1.07 × 10-6 M, a detection limit of 2.18 × 10-7 M, and a fast response of 6.5 s within the pH range of 2.5-8.5. The sensor was successfully used to determine HCQ purity in its raw material. The sensor represents a potential tool for rapid, sensitive, and selective monitoring of HCQ purity during industrial production from its starting materials.

A sustainable approach for the degradation kinetics study and stability assay of the SARS-CoV-2 oral antiviral drug Molnupiravir.

Molnupiravir (MPV) is the first direct-acting oral antiviral drug that effectively decreases nasopharyngeal infections with SARS-CoV-2 virus. The stability of MPV was tested by subjecting the drug to various stress conditions. The drug is liable to oxidative, acidic, and alkaline degradation and showed significant stability against thermal degradation. Mass spectrometry identified the degradation products and guided suggestion of the degradation patterns. Interestingly, while inspecting the UV-absorption spectra, we observed no absorbance at 270 nm for the products of the three degradation pathways (c.f. intact MPV). Direct spectrophotometry seemed a solution that perfectly fit the purpose of the stability assay method in our case. It avoids sophisticated instrumentation and complex mathematical data manipulation. The method determined MPV accurately (100.32% ± 1.62) and selectively (99.49% ± 1.63) within the linear range of 1.50 × 10-5-4.0 × 10-4 M and down to a detection limit of 0.48 × 10-5 M. The proposed method is simple and does not require any preliminary separation or derivatization steps. The procedure proved its validity as per the ICH recommendations. The specificity was assessed in the presence of up to 90% degradation products. The study evaluated the greenness profile of the proposed analytical procedure using the National Environmental Methods Index (NEMI), the Analytical Eco-Scale, and the Green Analytical Procedure Index (GAPI). The three metrics unanimously agreed that the developed procedure results in a greener profile than the reported method. The method investigated the degradation reactions' kinetics and evaluated the reaction order, rate constant, and half-life time for each degradation process.

A chemically modified solid-state sensor for magnesium(ii) ions and esomeprazole magnesium potentiometric assay.

The use of electrochemical sensors offers a simple, affordable solution with great reliability. Magnesium is a mineral that the body requires to function properly. It encourages preserving a stable pulse, strong bones, and healthy blood pressure. Herein, a novel ion-selective electrode using esomeprazole magnesium trihydrate as an ion-association complex was developed for magnesium(ii) ion determination in mineral water, drug substances, and pharmaceutical formulations. The electrode response was optimized in terms of plasticizer type, ion exchanger concentration, and membrane composition. To find the best sensor combination, the initial optimization research was performed using eight different sensors. A membrane containing 20% esomeprazole magnesium trihydrate, 36% carbon, and 44% o-Nitrophenyl Octyl Ether (NPOE) as a plasticizer yielded the best potentiometric response. The developed sensor demonstrated a Nernstian response with a slope of 29.93 ± 0.1 mV per decade in the concentration range of 1.41 × 10-5 mol L-1 to 1 × 10-2 mol L-1. Within a pH range of 5-8, it had a low detection limit of 4.13 × 10-6 mol L-1. When compared to the official method, there are no statistically significant differences.

Experimentally designed potentiometric sensor for green real-time and direct assay of hazardous bromate in bakery products.

Bakeries add extra potassium bromate to the dough to make homogeneous, elastic, fluffy bread. Bromate causes renal damage and cancer. FAO/WHO stated that bromate residues shouldn't be in baked products. A potentiometric sensor's membrane recipe was optimized for sensitive and selective bromate assay. We planned a custom experimental design of 21 sensors that included numerical and categorical factors (NPPE: PVC, matrix%, membrane thickness, and ionophore type). We defined sensor performance outcomes (Nernstian slope, quantification limit, correlation coefficient, response time and selectivity), and each sensor's outcome was determined. The computer software developed a predictive model for each outcome and the desirability function suggested the optimum sensor recipe. The sensor achieved a slope of -63.54 mV/decade and detection limit of 2 × 10-6 mol/L. The greenness profile was evaluated by the National Environmental Approach Index protocol. The developed sensor represents a reliable, fast, in-site tool for the assay of bromate in bakery products.

Experimentally designed electrochemical sensor for therapeutic drug monitoring of Ondansetron co-administered with chemotherapeutic drugs.

The experimental design extracts valuable information about the main effects and interactions from the least number of experiments. The current work constructs a solid-state sensor for selective assay of Ondansetron (OND) in pharmaceutical dosage form and plasma samples. During optimization, the Design Expert® statistical package constructed a custom design of 15 sensors with different recipes. We fed the software with the experimentally observed performance parameters for each sensor (slope, LOQ, correlation coefficient, and selectivity coefficient for sodium ions). The computer software analyzed the results to construct a prediction model for each response. The desirability function was adjusted to optimize the Nernstian slope, minimize the LOQ and selectivity coefficients, and maximize the correlation coefficient (r). The practical responses of the optimized sensor were close to those predicted by the model (slope = 60.23 mV/decade slope, LOQ = 9.09 × 10-6 M, r = 0.999, sodium selectivity coefficient = 1.09 × 10-3). The sensor successfully recovered OND spiked to tablets and human plasma samples with mean percentage recoveries of 100.01 ± 1.082 and 98.26 ± 2.227, respectively. Results were statistically comparable to those obtained by the reference chromatographic method. The validated potentiometric method can be used for fast and direct therapeutic drug monitoring of OND co-administered with chemotherapeutic drugs in plasma samples.

Experimentally designed chemometric models for the assay of toxic adulterants in turmeric powder.

Turmeric is an indispensable culinary spice in different cultures and a principal component in traditional remedies. Toxic metanil yellow (MY), acid orange 7 (AO) and lead chromate (LCM) are deliberately added to adulterate turmeric powder. This work compares the ability of multivariate chemometric models with those of artificial intelligent networks to enhance the selectivity of spectral data for the rapid assay of these three adulterants in turmeric powder. Using a custom experimental design, we provide a data-driven optimization for the sensitive parameters of the partial least squares model (PLS), artificial neural network (ANN) and genetic algorithm (GA). The optimized models are validated using sets of genuine turmeric samples from five different geographical regions spiked with standard adulterant concentrations. The optimized GA-PLS and GA-ANN models reduce the root mean square error of prediction by 18.4%, 31.1% and 55.3% and 25.0%, 69.9% and 88.4% for MY, AO and LCM, respectively.

Dual PI3K/Akt Inhibitors Bearing Coumarin-Thiazolidine Pharmacophores as Potential Apoptosis Inducers in MCF-7 Cells.

Breast cancer is the most common malignancy worldwide; therefore, the development of new anticancer agents is essential for improved tumor control. By adopting the pharmacophore hybridization approach, two series of 7-hydroxyl-4-methylcoumarin hybridized with thiosemicarbazone (V-VI) and thiazolidin-4-one moieties (VII-VIII) were prepared. The in vitro anticancer activity was assessed against MCF-7 cells adopting the MTT assay. Nine compounds showed significant cytotoxicity. The most promising compound, VIIb, induced remarkable cytotoxicity (IC50 of 1.03 + 0.05 µM). Further investigations were conducted to explore its pro-apoptotic activity demonstrating S-phase cell cycle arrest. Apoptosis rates following VIIb treatment revealed a 5-fold and 100-fold increase in early and late apoptotic cells, correspondingly. Moreover, our results showed caspase-9 dependent apoptosis induction as manifested by an 8-fold increase in caspase-9 level following VIIb treatment. Mechanistically, VIIb was found to target the PI3K-α/Akt-1 axis, as evidenced by enzyme inhibition assay results reporting significant inhibition of examined enzymes. These findings were confirmed by Western blot results indicating the ability of VIIb to repress levels of Cyclin D1, p-PI3K, and p-Akt. Furthermore, docking studies showed that VIIb has a binding affinity with the PI3K binding site higher than the original ligands X6K. Our results suggest that VIIb has pharmacological potential as a promising anti-cancer compound by the inhibition of the PI3K/Akt axis.

Impurity-profiling UPLC methods for quantitative analysis of some antiemetics formulated with pyridoxine.

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 C8 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.

The dynamic interplay between AMPK/NFκB signaling and NLRP3 is a new therapeutic target in inflammation: Emerging role of dapagliflozin in overcoming lipopolysaccharide-mediated lung injury.

Acute lung injury (ALI) is one the most common causes of morbidity and mortality in critically ill patients. In this study, we examined for first time the role of dapagliflozin (DPGZ) in lipopolysaccharide (LPS)-induced ALI in rats and determined the underlying molecular mechanisms by evaluating the effects of DPGZ on adenosine monophosphate kinase (AMPK), nuclear transcription factor kappa B, nucleotide-binding and oligomerization domain-like receptor 3 inflammasome activation. Treatment of acute lung injured rats with either low dose (5 mg/kg) or high dose (10 mg/kg) DPGZ significantly decreased oxidative stress by decreasing malondialdehyde and nitric oxide tissue levels with a significant increase in spectrophotometric measurements of superoxide dismutase, catalase, and reduced glutathione levels. DPGZ treatment resulted in a significant anti-inflammatory effect as indicated by suppression in myeloperoxidase activity, MCP-1, IL-1ß, IL-18, and TNF-α levels. DPGZ treatment also increased p-AMPK/t-AMPK with a significant reduction in NF-kB P65 binding activity and NFĸB p65 (pSer536) levels. These effects of DPGZ were accompanied by a significant reduction in NLRP3 levels and NLRP3 gene expression and a significant decrease in caspase-1 activity, which were also confirmed by histopathological examinations. We conclude that DPGZ antioxidant and anti-inflammatory activity may occur through regulation of AMPK/NFĸB pathway and inhibition of NLRP3 activation. These results suggest that DPGZ represents a promising intervention for the treatment of ALI, particularly in patients with type 2 diabetes.

Adoption of Advanced Chemometric Methods for Determination of Pyridoxine HCl, Cyclizine HCl, and Meclizine HCl in the Presence of Related Impurities: A Comparative Study.

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.

Secondary metabolites from Lantana camara L. flowers extract exhibit in vivo anti-urolithiatic activity in adult Wistar albino rats.

The present study aims at evaluating potential of the ethanol extracts of L. camara leaves (LE), flowers (FlE) and roots (RE) in the treatment of renal calculi and characterising the secondary metabolites in the active extract. The results revealed that the FlE had significantly reduced the levels of kidney parameters (calcium, creatinine, urea, and uric acid) against ethylene glycol (EG) injuries, and restored the activity of glutathione peroxidase (GPx), superoxide dismutase and lipid peroxide malondialdehyde to the normal level. In addition, FlE significantly attenuated iNOS tissue expression caused by EG. The results obtained in this study suggest the potential value of the L. camara L. flowers as an antiurolithiatic agent.

Acute and Delayed Doxorubicin-Induced Myocardiotoxicity Associated with Elevation of Cardiac Biomarkers, Depletion of Cellular Antioxidant Enzymes, and Several Histopathological and Ultrastructural Changes.

Doxorubicin (DOX; Adricin) is an anthracycline antibiotic, which is an efficient anticancer chemotherapeutic agent that targets many types of adult and pediatric tumors, such as breast cancer, leukemia, and lymphomas. However, use of DOX is limited due to its cardiotoxic effects. This study sequentially investigated the mechanistic pathways of the cardiotoxic process of DOX in rats at different post-treatment periods using cumulative dose, which is used in therapeutic regimes. In this regard, 56 male albino rats were used for the experiment. The experimental animals were divided into seven groups (n = 8/group) based on dose and sacrifice schedule as follows: G1 (2 mg/kg body weight [BW] and sacrificed at day 4), G2 (4 mg/kg BW and sacrificed at day 8), G3 (6 mg/kg BW and sacrificed at day 15), G4 (8 mg/kg BW and sacrificed at day 30), G5 (10 mg/kg BW and sacrificed at day 60), G6 (10 mg/kg BW and sacrificed at day 90), and G7 (10 mg/kg BW and sacrificed at day 120). As expected, G1, G2, and G3-treated groups revealed features of acute toxic myocarditis associated with degenerative and necrotic changes in myocytes, mitochondrial damage, elevation of cardiac biomarkers, and depletion of cellular antioxidant enzymes. However, these changes increased in severity with subsequent treatment with the same dose until reaching a cumulative dose of 10 mg/kg BW for 30 d. Furthermore, after a cumulative dose of 10 mg/kg BW with a withdrawal period of 2-3 months, various predominant changes in chronicity were reported, such as disorganization and atrophy of myocytes, condensation and atrophy of mitochondria, degranulation of mast cells, and fibrosis with occasional focal necrosis, indicating incomplete elimination of DOX and/or its metabolites. Altogether, these data provide interesting observations associated with the cardiotoxic process of DOX in rats that would help understand the accompanying changes underlying the major toxic effects of the drug. Future research is suggested to explore more about the dose-dependent mechanisms of such induced toxicity of DOX that would help determine the proper doses and understand the resulting cardiomyopathy.

Bone marrow-derived mesenchymal stem cells combined with gonadotropin therapy restore postnatal oogenesis of chemo-ablated ovaries in rats via enhancing very small embryonic-like stem cells.

BACKGROUND: Very small embryonic-like stem cells (VSELs) are a rare population within the ovarian epithelial surface. They contribute to postnatal oogenesis as they have the ability to generate immature oocytes and resist the chemotherapy. These cells express markers of pluripotent embryonic and primordial germ cells. OBJECTIVE: We aimed to explore the capability of VSELs in restoring the postnatal oogenesis of chemo-ablated rat ovaries treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) combined with pregnant mare serum gonadotropin (PMSG). METHODS: Female albino rats were randomly assigned across five groups: I (control), II (chemo-ablation), III (chemo-ablation + PMSG), IV (chemo-ablation + MSCs), and V (chemo-ablation + PMSG + MSCs). Postnatal oogenesis was assessed through measurement of OCT4, OCT4A, Scp3, Mvh, Nobox, Dazl4, Nanog, Sca-1, FSHr, STRA8, Bax, miR143, and miR376a transcript levels using qRT-PCR. Expression of selected key proteins were established as further confirmation of transcript expression changes. Histopathological examination and ovarian hormonal assessment were determined. RESULTS: Group V displayed significant upregulation of all measured genes when compared with group II, III or IV. Protein expression confirmed the changes in transcript levels as group V displayed the highest average density in all targeted proteins. These results were confirmed histologically by the presence of cuboidal germinal epithelium, numerous primordial, unilaminar, and mature Graafian follicles in group V. CONCLUSION: VSELs can restore the postnatal oogenesis in chemo-ablated ovaries treated by BM-MSCs combined with PMSG.

Evaluation of Synthetic 2,4-Disubstituted-benzo[g]quinoxaline Derivatives as Potential Anticancer Agents.

A new series of 2,4-disubstituted benzo[g]quinoxaline molecules have been synthesized, using naphthalene-2,3-diamine and 1,4-dibromonaphthalene-2,3-diamine as the key starting materials. The structures of the new compounds were confirmed by spectral data along with elemental microanalyses. The cytotoxic activity of all synthesized benzo[g]quinoxaline derivatives was assessed in vitro against the breast MCF-7 cancer cell line. The tested molecules revealed good cytotoxicity toward the breast MCF-7 cancer cell line, especially compound 3. The results of topoisomerase IIß inhibition assay revealed that compound 3 exhibits potent inhibitory activity in submicromolar concentration. Additionally, compound 3 was found to cause pre-G1 apoptosis, and slightly increase the cell population at G1 and S phases of the cell cycle profile in MCF-7 cells. Finally, compound 3 induces apoptosis via Bax activation and downregulation of Bcl2, as revealed by ELISA assay.

Albendazole-loaded cubosomes interrupt the ERK1/2-HIF-1α-p300/CREB axis in mice intoxicated with diethylnitrosamine: A new paradigm in drug repurposing for the inhibition of hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths worldwide. It was suggested that albendazole (ABZ) is a powerful inhibitor of several carcinoma types. However, the bioavailability of ABZ is very poor. Additionally, the mechanisms underlying the antitumor effects of ABZ may go beyond its tubulin-inhibiting activity. Therefore, we aimed to examine the effects of ABZ suspension (i.p. and p.o.) and ABZ-loaded cubosomes (LC) on the diethylnitrosamine-induced HCC in mice. ABZ-loaded nanoparticles exhibited a mean particle size of 48.17 ± 0.65 nm and entrapped 93.26 ± 2.48% of ABZ. The in vivo absorption study confirmed a two-fold improvement in the relative bioavailability compared with aqueous ABZ suspension. Furthermore, the oral administration of ABZ cubosomal dispersion demonstrated regression of tumor production rates that was comparable with ABZ (i.p.). ABZ relieved oxidative stress, improved liver function, and decreased necroinflammation score. The antiangiogenic activity was evident as ABZ effectively downregulated tissue expression of CD34, mRNA expression of CD309 and VEGF at the protein expression level. Besides, lower levels of MMP-9 and CXCR4 indicated antimetastatic activity. ABZ showed a considerable level of apoptotic activity as indicated by increased mRNA expression level of p53 and the increased Bax/BCL-2 ratio and active caspase-3. Additionally, Ki-67 expression levels were downregulated showing an antiproliferative potential. These protective effects contributed to increasing survival rate of diethylnitrosamine-treated mice. These effects found to be mediated via interrupting ERK1/2-HIF-1α-p300/CREB interactions. Therefore, our findings revealed that disrupting ERK1/2-HIF-1α-p300/CREB interplay might create a novel therapeutic target for the management of HCC.

Chemotherapeutic and chemopreventive potentials of ρ-coumaric acid - Squid chitosan nanogel loaded with Syzygium aromaticum essential oil.

One of the most important trends in chemotherapy is the development of green chemotropic drugs with maximal activity and minimal side effects. The nanoencapsulation of phytochemical oils with natural polymers has been documented as a promising approach to producing nanodrugs with sustainable bioactivity and prolonged stability. In this context, Syzygium aromaticum essential oil (SAEO) and ultrasound-assisted deacetylated chitosan (UCS3) were successfully extracted from clove buds and squid pens, respectively. Grafting of UCS3 by ρ-coumaric acid (ρCA) has been performed to fabricate the ρCACS nanogel which was used for nanoencapsulation of SAEO to yield SAEO-loaded nanogel (ρCACS@SAEO). The findings of spectral, thermal, and morphological analyses have confirmed the success of the formation of new materials and SAEO encapsulation, as well. Based on the findings of the in vitro antimicrobial, antioxidant, and anticancer studies, the nanoencapsulation of SAEO by ρCACS has significantly boosted its chemotherapeutic effects, compared to unencapsulated oil. Therefore, ρCACS@SAEO nanogel could be considered as a multifunctional chemotherapeutic/chemopreventive agent for prevention or therapy of pathologies induced by oxidative stress, microbial infection, and breast and skin cancer.

A Novel Combination Therapy Using Rosuvastatin and Lactobacillus Combats Dextran Sodium Sulfate-Induced Colitis in High-Fat Diet-Fed Rats by Targeting the TXNIP/NLRP3 Interaction and Influencing Gut Microbiome Composition.

Inflammasome targeting and controlling dysbiosis are promising therapeutic approaches to control ulcerative colitis. This report is the first to investigate the mechanisms underlying the coloprotective effects of rosuvastatin and Lactobacillus and their combined therapy on dextran sodium sulfate (DSS)-induced colitis in high-fat diet (HFD)-fed rats. Our results demonstrate the aggravation of intestinal inflammation as a consequence of an HFD following DSS administration. An association between dyslipidemia, LDL oxidation, CD36 expression, ROS generation, thioredoxin-interacting protein (TXNIP) upregulation, and NLRP3 inflammasome activation was demonstrated by DSS exposure in HFD-fed rats. We demonstrated that rosuvastatin/Lactobacillus significantly suppressed the DSS/HFD-induced increase in colon weight/length ratio, DAI, MDI, and myeloperoxidase, as well as corrected dysbiosis and improved histological characteristics. Additionally, caspase-1 activity and IL-1ß-driven pyroptotic activity was significantly reduced. Rosuvastatin/Lactobacillus showed prominent anti-inflammatory effects as revealed by the IL-10/IL-12 ratio and the levels of TNF-α and IL-6. These latter effects may be attributed to the inhibition of phosphorylation-induced activation of NF-κB and a concomitant reduction in the expression of NLRP3, pro-IL-1ß, and pro-IL-18. Furthermore, rosuvastatin/Lactobacillus reduced Ox-LDL-induced TXNIP and attenuated the inflammatory response by inhibiting NLRP3 inflammasome assembly. To conclude, rosuvastatin/Lactobacillus offers a safe and effective strategy for the management of ulcerative colitis.

Dual-Mode Gradient HPLC and TLC Densitometry Methods for the Simultaneous Determination of Paracetamol and Methionine in the Presence of Paracetamol Impurities.

BACKGROUND: Paracetamol (PC) is one of the most widely used analgesic and antipyretic drugs and has recently been integrated into the supportive therapy of COVID-19. Pharmaceuticals containing methionine (MT) with PC may contribute to avoid hepatotoxicity and eventual PC overdose-dependent death. OBJECTIVE: The current work purposes to develop and validate two chromatographic methods for the simultaneous determination of MT and PC in the presence of two PC impurities (4-nitrophenol [NP] and 4-aminophenol [AP]). METHOD: Two chromatographic methods were established and validated according to the International Conference on Harmonization guidelines. The first one was an RP-HPLC/UV method based on applying a "dual-mode" gradient elution. The separation was realized via varying both the composition of the ternary mobile phase (acetonitrile-methanol-water) and its flow rate. This strategy enabled a relatively rapid analysis with a satisfactory resolution, although the investigated compounds exhibit a significant difference in lipophilicity. The second one relied on TLC-densitometry, where the optimum separation was realized using a quaternary mobile phase system composed of butanol-dioxane-toluene-methanol (8:2.5:3.5:0.3, by volume). Both methods were monitored at 220 nm. RESULTS: The developed methods were proven to be robust, accurate, specific, and appropriate for the routine analysis of PC in its pure form or in pharmaceutical formulations with MT in quality control laboratories. CONCLUSIONS: The corresponding methods are suitable to determine MT and PC in the presence of PC impurities. HIGHLIGHTS: The study achieves the analysis of MT and PC in the presence of PC impurities via the application of HPLC and TLC-densitometry methods.

Solid-state potentiometric sensor for the rapid assay of the biologically active biogenic amine (tyramine) as a marker of food spoilage.

Tyramine (TYR) is a vasoactive biogenic amine found in food products due to improper storage and poor hygiene. High TYR intake results in a wide range of life-threatening physiological reactions. The work optimizes a solid-state potentiometric sensor in the absence of a reported potentiometric method for rapid and direct TYR assay. The optimization study included thirteen membrane cocktails of different compositions. The optimized sensor proved a near-Nernstian slope of 57.30 mV/decade, a quantification limit of 10.6 ppm, and a detection limit of 7.9 ppm. Validation results confirmed the sensor ability for the direct assay of TYR in blue cheese, aged cheese, Egyptian pickled cottage cheese, and pickled herring. A comparison with the reported chromatographic method expresses the merits and potentials of the developed sensor for the rapid testing of food edibility, quality, and safety based on its TYR content. Chemical compounds studied in this article: Tyramine (PubChem CID: 5610); Tyramine hydrochloride (PubChem CID: 66449); Poly(vinyl chloride) (PubChem SID: 24864273); Tricresyl phosphate (PubChem CID: 6529); sodium phosphotungstate tribasic hydrate (PubChem SID: 329753864).

Calixarene based portable sensor for the direct assay of indiscriminate ephedrine content of weight loss herbal preparations.

A novel potentiometric sensor was developed and optimized for the quantitative analysis of ephedrine in non-prescribed herbal supplements used as adjunctive therapy for weight loss. An initial optimization study aimed to reach the optimum membrane composition, sensor assembly, and experimental conditions. The study evaluated the effect of several factors on the sensor performance including different ion-exchangers, plasticizers, ionophores, membrane thicknesses, soaking solution concentrations, soaking time intervals, and pH. The optimized polyvinyl chloride membrane included tungstophosphoric acid hydrate as a cation exchanger, tricresyl phosphate as a plasticizer, and calix[8]arene as an ionophore to enhance the sensitivity and selectivity of the developed sensor. The polyvinyl chloride membrane was drop-casted over a polyaniline modified glassy carbon electrode surface to form a solid-state sensor. The proposed membrane succeeded to quantify ephedrine over a linear range of 6 × 10-6 to 1 × 10-2 M with a LOD of 3.60 × 10-6 M, acceptable selectivity, and fast response time. The IUPAC characterization of sensor response and International Conference on Harmonization validation parameters were calculated. The method successfully determined ephedrine concentration in spiked herbal mixtures and determined labeled and undeclared ephedrine content of weight loss herbal preparations.