A stability indicating RP-HPLC-UV assay method for the simultaneous determination of hydroquinone, tretinoin, hydrocortisone, butylated hydroxytoluene and parabens in pharmaceutical creams.

Multicomponent drugs are medications that combine two or more active pharmaceutical ingredients in a single dosage form. These dosage forms improve the patient compliance, reduce the risk of drug interactions, and simplify dosing regimens. However, quality control of these multicomponent dosage forms can be challenging, especially if the final product contains four or more ingredients that are active (comprise stabilizers, preservatives, excipients, and other components). This problem can be more pronounced if the excipients can interfere with the analysis. In this work, a stability indicating assay method was developed and validated (according to the ICH International Guidelines) for the simultaneous determination of hydroquinone (HQ), tretinoin (TRT), hydrocortisone (HCA), butylated hydroxytoluene (BHT), methyl paraben (MP) and propyl paraben (PP) in commercially available pharmaceutical creams. The proposed method is based on gradient elution using X-Bridge C18 (150 × 4.6 mm, 5 µm) column with a flow rate of 1 mL/min. The linear ranges (µg/mL) were 240-560 for HQ, 24-56 for MP, 132-308 for HCA, 6-14 for PP, 12-28 for BHT, 6.6-15 for TRT. During the validation process, the intra- and interday precision and trueness (evaluated as recovery) were found to be below 2.0% and between 100-102%, respectively. System suitability tests (SST) allow validating the herein proposed procedure specifically for pharmaceutical and industrial applications. SST test shows that the reported procedure fulfill with the Guidelines, allowing excellent separation of the analytes with very sensitive, accurate (precise and true) and reproducible quantitation of each analytes. The method was successfully applied in forced degradation studies of the six analytes. Specifically, acid degradation slightly affected HCA and BHT (91% recovery), while alkaline degradation drastically reduced HCA recovery (5.5%) and moderately affected BHT (85%). Photodegradation primarily influenced TRT quantity, and oxidative degradation intensified the BHT peak (130%).

Endothelin Receptor Blocker Reverses Breast Cancer-Induced Cardiac Remodeling.

Background: Although some cancer therapies have overt and/or subclinical cardiotoxic effects that increase subsequent cardiovascular risk in breast cancer patients, we have recently shown that the breast tumor itself can also induce cardiac hypertrophy through the activation of the endothelin system to contribute to cardiovascular risk. However, the extent to which the suppression of the activation of the endothelin system could improve cardiac remodeling in breast cancer patients has yet to be investigated. Objectives: We aimed to retrospectively assess the cardiac morphology/function in patients with breast cancer before receiving cancer chemotherapy and to investigate if the suppression of the activation of the endothelin system improves cardiac remodeling in a mouse model of breast cancer. Methods: Our study involved 28 previously studied women with breast cancer (including 24 after tumor resection) before receiving adjuvant therapy and 17 control healthy women. In addition, we explored how the endothelin system contributed to breast cancer-induced cardiac remodeling using a mouse model of breast cancer. Results: Our results indicate that before chemotherapy, breast cancer patients already exhibit relative cardiac remodeling and subclinical cardiac dysfunction, which was associated with the activation of the endothelin system. Importantly, our mouse data also show that the endothelin receptor blocker atrasentan significantly lessened cardiac remodeling and improved cardiac function in a preclinical model of breast cancer. Conclusions: Although our findings should be further examined in other preclinical/clinical models, our data suggest that endothelin receptor blockers may play a role in cardiac health in individuals with breast cancer. (Understanding and Treating Heart Failure With Preserved Ejection Fraction: Novel Mechanisms, Diagnostics and Potential Therapeutics [Alberta HEART]; NCT02052804 and Multidisciplinary Team Intervention in Cardio-Oncology [TITAN]; NCT01621659).

A prospective randomized controlled study on the role of restoring liver diaphragm surface tension and pain control at port sites in optimizing pain management following laparoscopic cholecystectomy.

Introduction: After laparoscopic cholecystectomy (LC), pain is still a significant concern leading to extended hospital stays or readmissions. A standardized strategy is needed to offer effective pain relief postoperatively. The pain in the early postoperative period is mainly due to elimination of intraperitoneal surface tension. The aim of this study is to evaluate the restoration of intraabdominal surface tension and the use of bupivacaine-soaked tachosil to control parietal abdominal pain at the port sites to optimize postoperative pain management. Patients and methods: Between March 2020 to December 2021, 816 patients undergoing LC were randomized into two groups after exclusion of 12 patients: Group A-interventional contained 402 patients; Group B-control contained 402 patients. Data to be compared were made in terms of operative time, shoulder pain, upper abdominal pain, and number of analgesic doses and hospital stay. Pain intensity was assessed by using the visual analog scale. Results: There was no significant variation in the demographic data between the two groups. There was significant statistical difference between Groups (A) and (B) regarding severity of shoulder pain and port site pain and number of analgesic doses and hospital stay in favor of Group (A). The results were evaluated within 95% confidence intervals and significance was determined as P < .05. Conclusion: The restoration of intraabdominal surface tension by absorbing as much CO2 as possible at the end of laparoscopic cholecystectomy via the epigastric port route, as well as the use of bupivacaine-soaked tachosil to control parietal abdominal pain at the port sites; both steps significantly improved postoperative pain management, reduced the number of analgesic doses, and decreased the length of hospital stay.

Cooking with EDTA reduces nutritional value of Vicia faba beans.

Ethylenediamine terta-acetic acid (EDTA) used to accelerate the cooking process of Vicia (V. faba) beans. In this study, the effect of cooking with EDTA on the nutritional value of V. faba beans was addressed. Water contents, total proteins, lipids, carbohydrates, minerals and amino acids were determined before and after boiling with EDTA (2 g/L). In both of whole beans and seed coats, the water content was increased after boiling with EDTA. In contrast, the levels of proteins, lipids and carbohydrates were significantly decreased in both the whole beans and seed coats upon boiling with EDTA. Furthermore, the levels of sodium were increased while, the levels of other minerals were decreased. All amino acids were significantly decreased in the whole beans and increased in the seed coats after boiling with EDTA. EDTA addition to V. faba beans during the cooking process decreased the nutritional value of the cooked V. faba beans.

Promoter methylation and expression of DNA repair genes MGMT and ERCC1 in tissue and blood of rectal cancer patients.

Rectal cancer involves one-third of colorectal cancers (CRCs). Recently, data supported that DNA methylation have a role in CRC pathogenesis. In the present study we aimed to analyze the methylation status of MGMT and ERCC1 promoter regions in blood and tissue of patients with benign and malignant rectal tumors. We also studied the methylated MGMT and ERCC1 genes and their relations with clinicopathological features. Furthermore, we suggested that methylation may play a critical function in the regulation of MGMT and ERCC1 expression. Fifty patients with non-metastatic cancer rectum and 43 patients with benign rectal lesions were involved in the study. DNA extraction from blood and rectal specimens was done to analyze the methylation status of MGMT and ERCC1 genes by methylation-specific PCR method. RNA was extracted also to determine the expression levels of these genes by real time-PCR. The frequency of MGMT and ERCC1 methylation was significantly higher in rectum cancers than in benign tumors both for the tissue and the blood (p<0.001). There was no relation between MGMT or ERCC1 methylation and clinicopathological features; while they were correlated with the response to therapy. An interesting finding that the agreement of the methylation levels in the blood and rectal tissue was classified as good (κ=0.78) for MGMT gene and as very good (κ=0.85) for ERCC1. Lastly, the MGMT and ERCC1 genes methylation was associated with down-regulation of their mRNA expression when compared with the non-methylated status. Our findings provided evidence that both blood and tumor tissue MGMT and ERCC1 methylation were associated with cancer rectum. MGMT or ERCC1 methylation in blood could be suitable non-invasive biomarkers differentiating benign and malignant rectal tumors. Furthermore, the methylation of the MGMT and ERCC1 promoter regions was associated with down-regulation of their mRNA expression.

Simultaneous Determination of Ursodeoxycholic Acid and Chenodeoxycholic Acid in Pharmaceutical Dosage Form by HPLC-UV Detection.

A reversed-phase HPLC method was developed for the simultaneous determination of ursodeoxycholic acid (UDCA) and the epimeric isomer, chenodeoxycholic acid (CDCA), in their synthetic mixtures and in tablet dosage form. The proposed HPLC method uses a C18 column and mobile phase consisting of an acetonitrile-phosphate buffer mixture (pH 2.3, 100 mM; 50 + 50, v/v) at a flow rate of 2.0 mL/min with UV detection at 210 nm. The method was validated according to the International Conference on Harmonization guidelines; and linearity, range, accuracy, precision, robustness, and system suitability were studied. The LOD and LOQ were also calculated and found to be 1.23 and 3.73 µg/mL for UDCA and 0.83 and 2.52 µg/mL for CDCA, respectively. The method was adapted for UHPLC, in which baseline separation was achieved in <2.5 min. The assay results of Ursomix tablets by the developed method were statistically compared with those obtained by the reference method using t- and F-tests, and no significant differences were observed.

Pharmaceutical and biomedical applications of dispersive liquid-liquid microextraction.

Sample treatment is so crucial in pharmaceutical and biomedical analysis. Proper sample preparation protects the analytical instrument, increases the sensitivity, and enhances the selectivity by removing probable interfering substances. Dispersive liquid-liquid microextraction (DLLME) is one of the most important approaches in sample treatment. In normal DLLME, the organic droplet of the extractant is mixed with a dispersing solvent before being injected into the sample. After manual or mechanical shaking, the cloudy solution is centrifuged to break the formed emulsion. The organic phase is then separated and transferred to the analytical instrument. The dispersion process employed in DLLME dramatically increases the contact surface between the extractant and the sample, which enhances the extraction kinetics and efficiency. DLLME can be classified based on the dispersion technique or the density of the extractant. Accordingly, different modes of DLLME have evolved and been applied for drug analysis in biological fluids. This review discusses the principle of DLLME, the requirements of organic solvents used as extractants in each mode and the different factors affecting the extraction efficiency. Selected applications of the different DLLME modes in bio-pharmaceutical analysis have also been presented.

Distal renal tubular acidosis, hypokalemic paralysis, nephrocalcinosis, primary hypothyroidism, growth retardation, osteomalacia and osteoporosis leading to pathological fracture: a case report.

Renal tubular acidosis (RTA) is a constellation of syndromes arising from different derangements of tubular acid transport. Recent advances in the biology of urinary acidification have allowed us to discern various molecular mechanisms responsible for these syndromes. RTA often presents as renal stone disease with nephrocalcinosis, ricket/osteomalacia and growth retardation in children with ultimate short stature in adulthood. The case reported here has features of distal renal tubular acidosis (dRTA), hypokalemic paralysis, primary hypothyroidism, growth retardation, osteomalacia and osteopenia leading to stress fracture. All these features presenting in a single case (as in our case) is a rare occurrence, so far other cases of distal renal tubular acidosis (dRTA) have been reported.