Race as a determinant of prenatal depressive symptoms: analysis of data from the 'All Our Families' study.

OBJECTIVES: Prenatal depression is a serious maternal-child health concern. Risk factors and health consequences appear more prevalent in Indigenous communities and ethnic minority groups; however, research on these populations is limited. We examined the following questions: (A) How do pregnant Indigenous women, ethnic minority women, and White women compare on levels of depressive symptoms and possible clinical depression, and on major risk and protective factors? (B) Is non-dominant (non-White) race associated with higher depressive symptoms and possible clinical depression? (C) What factors mediate and moderate the relationship between race and depression? DESIGN: Data were from the All Our Families study (n = 3354 pregnant women from Alberta, Canada). Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Descriptive statistics and multivariable regression methods were used to assess the hypotheses that Indigenous and ethnic minority women would have significantly higher mean EPDS score estimates and higher proportions scoring above cut-offs for possible clinical depression, relative to White women. The association between race and depressive symptoms was hypothesised to be partially mediated by risk factors of socioeconomics, health background, discrimination, domestic violence, and psychosocial stress. Potential confounders were age, marital status, and parity. Diet and social support were hypothesised as protective buffers between stress and depressive symptoms. RESULTS: A higher proportion of White women were married, had family income over $80,000, were employed, and had adequate social support, relative to other women. They had significantly lower mean depressive symptom score, and a smaller proportion scored above cut-offs for possible clinical depression. The positive association between race and depressive symptoms appeared to be partially mediated by socioeconomic factors and psychosocial stress. Social support appeared to moderate the association between stress and depressive symptoms. CONCLUSIONS: Strategies to address socioeconomic status, stress, and social support among racialized minority women may reduce the risk for prenatal depression.

Effect of Solvent on the Optical Rotation of Azatryptophan Derivatives.

Chirally pure enantiomers of differently protected 7-azatryptophan derivatives (R-3c, S-3c, R-3i, S-3i, R-3m, S-3m, R-3aa, and S-3aa) were synthesized, which showed solvent-dependent optical rotation. The obtained results not only exhibited changes in the values but also showed the variation in sign (- or +) with the different solvents studied. The change in optical rotation value was essentially attributed to the electron-donating property, which can be correlated to the donor number of the solvents. There are two types of hydrogen bonds, intramolecular (i.e., form within the structure) and intermolecular (i.e., form with external groups such as solvents). These hydrogen bonds are responsible for the value and sign variations, and 1H NMR experiments were used to further characterize them. The NMR data suggested that hydrogen bond formation is occurring between the Fmoc NH group vicinal to the chiral center and donor group of the corresponding solvent.

Antagonistic Roles of Gallates and Ascorbic Acid in Pyomelanin Biosynthesis of Pseudomonas aeruginosa Biofilms.

Primarily synthesized for chelating metal ions from the surrounding media, the pyomelanin plays an important role in bacterial virulence where it is needed for infection and biofilm formation as well as protection from host immune response. In this study, two out of three phenolic acids, gallic acid, and propyl gallate induced pyomelanin in two clinical isolates of Pseudomonas aeruginosa and inhibited biofilm formation. Ascorbic acid treatment reversed the gallic acid and propyl gallate mediated pyomelanin synthesis without reversing the inhibition of the biofilm formation. mRNA expression study revealed the upregulation of homogentisic acid oxidase enzyme by ascorbic acid treatment, possibly contributing towards the inhibition of pyomelanin synthesis. Tannic acid did not show any antibacterial or pyomelanin-induction activities. The synergistic effect of gallates and ascorbic acid in the inhibition of biofilm formation and associated pyomelanin synthesis was evidenced which needs further studies to establish their antibacterial efficacies, especially against the clinical isolates of Pseudomonas sp.

Membrane Depolarization Sensitizes Pseudomonas aeruginosa Against Tannic Acid.

The use of dietary polyphenols as antimicrobial agents has gained immense popularity in recent years, although few of them-like tannic acid has limited use in this field of research; one of the main reasons is its restricted access through the bacterial membrane. Dissipating the bacterial membrane potential with a sub-lethal dosage of the protonophore, carbonyl cyanide m-chlorophenyl hydrazone, enhanced the tannic acid-cytotoxicity with subsequent inhibition of aerobic respiration in Pseudomonas aeruginosa strains which otherwise exhibited a minimum response to tannic acid. However, ascorbic acid, an antioxidant and bacterial membrane-stabilizing compound, had rescued the cells from both tannic acid- and CCCP-mediated lethality. The results suggested that dispersing the membrane potential with a protonophore can enhance the antibacterial properties of tannic acid.

Combination of Foley and prostaglandins versus Foley and oxytocin for cervical ripening: a network meta-analysis.

BACKGROUND: Trial and meta-analysis data revealed a reduction in time to delivery for Foley and prostaglandins or Foley and oxytocin vs Foley alone. However, there are limited data for the comparison of the 2 combination methods against each other. OBJECTIVE: This study aimed to determine whether Foley and prostaglandins or Foley and oxytocin decrease the time to vaginal delivery using a network meta-analysis. STUDY DESIGN: A network meta-analysis (PROSPERO CRD42018081948) was performed comparing Foley and prostaglandins (prostaglandin E1 or prostaglandin E2) vs Foley and oxytocin for cervical ripening. Foley alone and prostaglandins alone were used as nodes for indirect comparison. Database searches were performed from inception to March 2020 with data abstracted from published manuscripts. Eligibility criteria included randomized trials comparing Foley and oxytocin with Foley and prostaglandins (misoprostol or dinoprostone). Trials that compared Foley catheter or prostaglandins with a combination of Foley and prostaglandins or Foley and concurrent oxytocin were also included. Nulliparous and multiparous women were analyzed together. Foley catheters of any catheter material or size and >24 weeks' gestational age with a live fetus were included. Quasi-randomized, cohorts, and other combination methods for cervical ripening were not included. Prostaglandin E1 and prostaglandin E2 combined methods were analyzed separately in a planned subanalysis. The primary outcome was the mean time from induction to vaginal delivery in hours. Secondary outcomes included time from induction to delivery, delivery within 24 hours, cesarean delivery, chorioamnionitis, endometritis, epidural use, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admission, and 5-minute appearance, pulse, grimace, activity, and respiration score of <7. Data were analyzed as a network meta-analysis using multivariate meta-regression. RESULTS: A total of 30 randomized controlled trials with a total of 6465 women were considered eligible for inclusion in this network meta-analysis. When compared with Foley alone, the use of Foley-oxytocin reduced the time to vaginal delivery by 4.2 hours (mean duration, -4.2 hours; 95% confidence interval, -6.5 to -1.9). Foley-prostaglandins reduced the time to vaginal delivery compared with Foley but did not meet statistical significance (mean duration, -2.9 hours; 95% confidence interval, -5.7 to 0.0; P=.05). When compared head-to-head, there was no difference in the time to vaginal delivery between Foley-prostaglandins and Foley-oxytocin (mean duration, 1.3 hours; 95% confidence interval, -2.0 to 4.7). There was no difference in the rate of cesarean delivery, chorioamnionitis, epidural, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admissions, or 5-minute appearance, pulse, grimace, activity, and respiration score of <7 for Foley-prostaglandins vs Foley-oxytocin, although the rate of endometritis was high for Foley-prostaglandins. In the subanalysis by prostaglandin type, there was no difference in the time to vaginal delivery for Foley-misoprostol vs Foley-dinoprostone vs Foley-oxytocin. However, Foley-dinoprostone had a definite trend toward longer time to all deliveries compared with that of both Foley-misoprostol and Foley-oxytocin (P=.05). CONCLUSION: Time to vaginal delivery was similar when comparing Foley with combined misoprostol, combined dinoprostone, and combined oxytocin. Dinoprostone comparisons are limited by small sample size but suggest longer time to delivery compared with Foley and misoprostol or oxytocin. No significant differences were observed in maternal or neonatal adverse events except for endometritis, but this was limited by the sample size, varied reporting of studies used in the indirect comparisons, and definitions of infectious morbidity use in the studies.

Synthesis of Differentially Protected Azatryptophan Analogs via Pd2(dba)3/XPhos Catalyzed Negishi Coupling of N-Ts Azaindole Halides with Zinc Derivative from Fmoc-Protected tert-Butyl (R)-2-Amino-3-iodopropanoate.

Unnatural amino acids play an important role in peptide based drug discovery. Herein, we report a class of differentially protected azatryptophan derivatives synthesized from N-tosyl-3-haloazaindoles 1 and Fmoc-protected tert-butyl iodoalanine 2 via a Negishi coupling. Through ligand screening, Pd2(dba)3/XPhos was found to be a superior catalyst for the coupling of 1 with the zinc derivative of 2 to give tert-butyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)propanoate derivatives 3 in 69-91% isolated yields. In addition, we have demonstrated that the protecting groups, namely, Ts, Fmoc, and tBu, can be easily removed selectively.

Subcellular compartmentalization of glutathione peroxidase 1 allelic isoforms differentially impact parameters of energy metabolism.

Specific genetic variations in the gene for the selenium-containing antioxidant protein glutathione peroxidase 1 (GPX1) are associated with the risk of a variety of common diseases, including cancer, diabetes, and cardiovascular disorders. Two common variations have been focused upon, one resulting in leucine or proline at codon 198 and another resulting in 5, 6, or 7 alanine repeats were previously shown to affect the distribution of GPX1 between the cytoplasm and mitochondria. Human MCF7 cells engineered to exclusively express GPX1 with five alanine repeats at amino terminus and proline at codon 198 (A5P) and seven alanine repeats at amino terminus and leucine at codon 198 (A7L), as well as derivatives targeted to the mitochondria by the addition of a mitochondrial localization sequence (mA5P and mA7L) were used to assess the consequences of the expression of these proteins on the cellular redox state and bioenergetics. Ectopic expression of A5P and A7L reduced the levels of reactive oxygen species, and the mitochondrially targeted derivatives exhibited better activity in these assays. Bioenergetics and mitochondrial integrity were assessed by measuring mitochondrial membrane potential, oxygen consumption, adenosine triphosphate (ATP) levels, and the levels of lactate dehydrogenase. The results of these assays indicated distinctively, and sometimes opposing, patterns with regard to differences between the consequences of the expression of A5P, A7L, mA5P, and mA7L. These data provide new information on the consequences of differences in the primary structure and cellular location of GPX1 proteins and contribute to the understanding of how these effects might contribute to human disease.

MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility.

MEKK1 (also known as MAP3K1), which plays a major role in MAPK signaling, has been implicated in mechanical processes in cells, such as migration. Here, we identify the actin-binding protein calponin-3 as a new MEKK1 substrate in the signaling that regulates actomyosin-based cellular contractility. MEKK1 colocalizes with calponin-3 at the actin cytoskeleton and phosphorylates it, leading to an increase in the cell-generated traction stress. MEKK1-mediated calponin-3 phosphorylation is attenuated by the inhibition of myosin II activity, the disruption of actin cytoskeletal integrity and adhesion to soft extracellular substrates, whereas it is enhanced upon cell stretching. Our results reveal the importance of the MEKK1-calponin-3 signaling pathway to cell contractility.

CAF cellular glycolysis: linking cancer cells with the microenvironment.

Cancers have long being hallmarked as cells relying heavily on their glycolysis for energy generation in spite of having functional mitochondria. The metabolic status of the cancer cells have been revisited time and again to get better insight into the overall carcinogenesis process which revealed the apparent crosstalks between the cancer cells with the fibroblasts present in the tumour microenvironment. This review focuses on the mechanisms of transformations of normal fibroblasts to cancer-associated fibroblasts (CAF), the participation of the CAF in tumour progression with special interest to the role of CAF cellular glycolysis in the overall tumorigenesis. The fibroblasts, when undergoes the transformation process, distinctly switches to a more glycolytic phenotype in order to provide the metabolic intermediates necessary for carrying out the mitochondrial pathways of ATP generation in cancer cells. This review will also discuss the molecular mechanisms responsible for this metabolic make over promoting glycolysis in CAF cells. A thorough investigation of the pathways and molecules involved will not only help in understanding the process of activation and metabolic reprogramming in CAF cells but also might open up new targets for cancer therapy.

Assessing biochemical changes during standardization of fermentation time and temperature for manufacturing quality black tea.

In black tea manufacturing, one of the most important steps is fermentation which influences the quality of tea. The macerated tea leaves were fermented at various temperatures (20, 25, 30, 35 °C) for different duration. Changes in polyphenoloxidase and peroxidase activities, depletion patterns of individual catechins, differences in individual theaflavin levels and formation of thearubigins were measured in leaves during fermentation. Higher stability of polyphenoloxidase and peroxidase enzymes was observed at lower temperature (20 °C), and increase in temperature, led to enzyme instability. The rate of degradation of all the catechins was found to be fastest at 35 °C and slowest at 20 °C. The formation and depletion of individual theaflavins varied with temperature and fermentation duration. The time required for the formation of maximum total theaflavins (TF) was highest at lower temperature and this time duration also varied for different theaflavins formation. Maximum amount of thearubigins (TR) content and liquor colour development was observed at 35 °C, and decrease in temperature reduced thearubigins accumulation. However, maximum brightness as well as TF/TR ratio was obtained at 20 °C, which suggests that fermentation at lower temperature is suitable for manufacturing quality black tea.

Unleashing the power of polymeric nanoparticles - Creative triumph against antibiotic resistance: A review.

Antibiotic resistance (ABR) poses a universal concern owing to the widespread use of antibiotics in various sectors. Nanotechnology emerges as a promising solution to combat ABR, offering targeted drug delivery, enhanced bioavailability, reduced toxicity, and stability. This comprehensive review explores concepts of antibiotic resistance, its mechanisms, and multifaceted approaches to combat ABR. The review provides an in-depth exploration of polymeric nanoparticles as advanced drug delivery systems, focusing on strategies for targeting microbial infections and contributing to the fight against ABR. Nanoparticles revolutionize antimicrobial approaches, emphasizing passive and active targeting. The role of various molecules, including small molecules, antimicrobial peptides, proteins, carbohydrates, and stimuli-responsive systems, is being explored in recent research works. The complex comprehension mechanisms of ABR and strategic use of nanotechnology present a promising avenue for advancing antimicrobial tactics, ensuring treatment efficacy, minimizing toxic effects, and mitigating development of ABR. Polymeric nanoparticles, derived from natural or synthetic polymers, are crucial in overcoming ABR. Natural polymers like chitosan and alginate exhibit inherent antibacterial properties, while synthetic polymers such as polylactic acid (PLA), polyethylene glycol (PEG), and polycaprolactone (PCL) can be engineered for specific antibacterial effects. This comprehensive study provides a valuable source of information for researchers, healthcare professionals, and policymakers engaged in the urgent quest to overcome ABR.

Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.

Organogels: "GelVolution" in Topical Drug Delivery - Present and Beyond.

Topical drug delivery holds immense significance in dermatological treatments due to its non-invasive nature and direct application to the target site. Organogels, a promising class of topical drug delivery systems, have acquired substantial attention for enhancing drug delivery efficiency. This review article aims to explore the advantages of organogels, including enhanced drug solubility, controlled release, improved skin penetration, non-greasy formulations, and ease of application. The mechanism of organogel permeation into the skin is discussed, along with formulation strategies, which encompass the selection of gelling agents, cogelling agents, and additives while considering the influence of temperature and pH on gel formation. Various types of organogelators and organogels and their properties, such as viscoelasticity, non-birefringence, thermal stability, and optical clarity, are presented. Moreover, the biomedical applications of organogels in targeting skin cancer, anti-inflammatory drug delivery, and antifungal drug delivery are discussed. Characterization parameters, biocompatibility, safety considerations, and future directions in optimizing skin permeation, ensuring long-term stability, addressing regulatory challenges, and exploring potential combination therapies are thoroughly examined. Overall, this review highlights the immense potential of organogels in redefining topical drug delivery and their significant impact on the field of dermatological treatments, thus paving the way for exciting prospects in the domain.

Nano-Innovations in Cancer Therapy: The Unparalleled Potential of MXene Conjugates.

MXenes are two-dimensional transition metal carbides, nitrides, and carbonitrides that have become important materials in nanotechnology because of their remarkable mechanical, electrical, and thermal characteristics. This review emphasizes how crucial MXene conjugates are for several biomedical applications, especially in the field of cancer. These two-dimensional (2D) nanoconjugates with photothermal, chemotherapeutic, and photodynamic activities have demonstrated promise for highly effective and noninvasive anticancer therapy. MXene conjugates, with their distinctive optical capabilities, have been employed for bioimaging and biosensing, and their excellent light-to-heat conversion efficiency makes them perfect biocompatible and notably proficient nanoscale agents for photothermal applications. The synthesis and characterization of MXenes provide a framework for an in-depth understanding of various fabrication techniques and their importance in the customized formation of MXene conjugates. The following sections explore MXene-based conjugates for nanotheranostics and demonstrate their enormous potential for biomedical applications. Nanoconjugates, such as polymers, metals, graphene, hydrogels, biomimetics, quantum dots, and radio conjugates, exhibit unique properties that can be used for various therapeutic and diagnostic applications in the field of cancer nanotheranostics. An additional layer of understanding into the safety concerns of MXene nanoconjugates is provided by detailing their toxicity viewpoints. Furthermore, the review concludes by addressing the opportunities and challenges in the clinical translation of MXene-based nanoconjugates, emphasizing their potential in real-world medical practices.

A unifying framework for depression: bridging the major biological and psychosocial theories through stress.

Several mechanisms for the development of depression have been proposed, and a comparative examination reveals considerable overlap. This paper begins by summarizing the conclusions drawn in the literature on the major biological theories: HPA-axis hyperactivity, the monoamine theory, the cytokine hypothesis/ macrophage theory, and structural changes to relevant brain regions and neurons. It then discusses the role of psychosocial stress as a bridge between the pathophysiology of depression and its predominantly psychosocial risk factors, touching upon theories offered in psychology and in population health. This paper further proposes a unifying framework which integrates the major theories. The multiple systems involved, and the directional complexity among them, likely help to explain the wide-ranging symptoms associated with depression, and the wide variety of comorbid medical conditions. They may also contribute to challenges in treatment, the diversity in symptoms and treatment outcomes among individuals, and the high rates of symptom persistence and relapse. The apparent bi-directionality of associations may suggest the existence of positive-feedback loops which aggravate symptoms; however, further bench research is required to confirm such phenomena. A better understanding of these interweaving associations is warranted. Additionally, given the significant influence of socioeconomic and psychosocial factors on the aetiology of depression, population-level interventions that address the social determinants of health are required. Current individual-level pharmacologic approaches are designed to treat pathophysiology once it is underway, and current individual-level non-pharmacologic interventions (such as talk therapy) are designed to moderate the relationship between psychosocial stress and pathophysiology. In contrast, a key strategy for primary prevention lies in population-level interventions that address the predominantly social causes of one of depression's most notable risk factors: chronic psychosocial stress.

Promising practices for the design and implementation of sexuality education programmes for youth in India: a scoping review.

Sexual violence and HIV/AIDS are major public health concerns in India. By promoting bodily autonomy, wellbeing, and dignity through knowledge and skills, comprehensive sexuality education for young people can help prevent adverse sexual and reproductive health outcomes. While there is increased recognition globally regarding young people's need for sexuality education, translating this recognition into accepted programmes in India has been challenging. This scoping review aims to examine recommendations for promising practices for the design and implementation of sexuality education programmes and resources aimed at youth in India. A systematic search and review of the literature was conducted from June to August 2020. Of the total 5312 citations identified and screened, 622 advanced to full-text screening, and 39 were included in the final analysis. Promising practices include the need to: tailor content to serve the needs of the specific youth population being targeted; use engaging and participatory methods to teach sexual health content; work in partnership and collaboration with local experts and organisations; address potential barriers to participation and work to mitigate those barriers for marginalised youth; be youth friendly, flexible and convenient; and to be developmentally and culturally appropriate for the Indian youth context. Sexuality education programmes should integrate into existing community services and link with local reproductive health services to help provide youth with access to the services they may need. Continued work and efforts are required to address the interrelated and broad structural factors, including political, financial, social, and cultural factors that affect youth sexual health and wellbeing.

Ameliorative anticancer effect of dendrimeric peptide modified liposomes of letrozole: In vitro and in vivo performance evaluations.

Letrozole (LTZ) loaded dendrimeric nano-liposomes were prepared for targeted delivery to breast cancer cells. Surface modification with cationic peptide dendrimers (PDs) and a cancer specific ligand, transferrin (Tf), was attempted. Arginine-terminated PD (D-1) and Arginine-terminated, lipidated PD (D-2) were synthesized using Solid Phase Peptide Synthesis, purified by preparative HPLC and characterized using 1HNMR, MS and DSC analyses. Surface modification of drug loaded liposomes with Tf and/or PD was carried out. Formulations were characterized using FTIR, DSC, 1HNMR, XRD and TEM. Tf-conjugated LTZ liposomes (LTf) and Tf/D-2-conjugated LTZ liposomes (LTfD-2) showed greater cytotoxic potential (IC50 = 95.03 µg/mL and 23.75 µg/mL respectively) with enhanced cellular uptake in MCF7 cells compared to plain LTZ. Blocking studies of Tf (Tf-receptor mediated internalization) revealed decreased uptake of LTf and LTfD-2 confirming the role of Tf in uptake of Tf-conjugated liposomes. Intravenous treatment with LTfD-2 caused highest reduction in tumor volumes of female BALB/c-nude mice (145 mm3) compared to plain LTZ (605 mm3) and unconjugated LTZ liposomes (LP) (300 mm3). In vivo biodistribution studies revealed higher fluorescence in tumor tissue and liver of LTfD-2 treated mice than LTf or LP treatment. Immunohistochemical studies revealed greater apoptotic potential of LTfD-2 as indicated by TUNEL assay and ROS detection assay. The study reveals the superior therapeutic efficacy of the developed LTZ liposomal nanocarriers using PDs to enhance the transfection efficiency in addition to modifying the surface characteristics by attaching a targeting ligand for active drug targeting to breast cancer cells.

Isolation and characterization of pseudo degradation products of acalabrutinib using ESI-HRMS/MS and NMR: Formation of possible geometrical isomers.

A forced degradation study of acalabrutinib (ACB), used to treat relapsed mantle cell lymphoma, was performed to identify and characterize all possible major degradation products formed under different stress conditions. The degradation products (DP) were separated using reverse phase UHPLC system on Kinetex EVO C18 column. Major DPs formed were isolated using semi-preparative HPLC and characterized by LC-ESI-HRMS/MS and NMR. ACB degraded to form seven major degradants (DP-I to DP-VII). DP-I and DP-V were formed under alkaline stress condition, whereas DP-II, DP-III, DP-VI and DP-VII were formed under both acidic and basic conditions. Further, DP-IV was formed when ACB drug was exposed to hydrogen peroxide stress condition. ACB was found to be stable when subjected to aqueous (neutral pH), thermal and UV radiation of 254 nm, as it has not shown any significant degradation under these conditions. Interestingly, two pairs of pseudo geometrical isomeric DPs (DP-II and DP-III, DP-VI and DP-VII) were observed. The plausible degradation pathway of ACB and fragmentation patterns of both ACB and major DPs were discussed.

A strategy for evaluation of isotopic enrichment and structural integrity of deuterium labelled compounds by using HR-MS and NMR.

Determining the purity of deuterium labelled compounds is important due to the increasing use of these compounds in mass spectrometry (MS) based quantitative analyses for targeting metabolic flux, reducing toxicity, confirming reaction mechanisms during synthesis, predicting enzyme mechanisms, and enhancing the efficacy of drugs, in quantitative proteomics, and also as internal standards. In the present study, a strategy using liquid chromatography electrospray ionization high resolution mass spectrometry (LC-ESI-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy was proposed to determine the isotopic enrichment and structural integrity of deuterium labelled compounds. The proposed strategy involves recording full scan MS, extracting and integrating isotopic ions, and calculating the isotopic enrichment of the desired labelled compounds. NMR analysis confirms structural integrity or positions of labelled atoms and can provide insights into the relative percent isotopic purity. This strategy was used to evaluate the isotopic enrichment and structural integrity of in-house synthesized compounds as well as a series of commercially available deuterium labelled compounds. The % isotopic purity for labelled compounds of a benzofuranone derivative (BEN-d2), tamsulosin-d4 (TAM-d4), oxybutynin-d5 (OXY-d5), eplerenone-d3 (EPL-d3), and propafenone-d7 (PRO-d7) was calculated and found to be 94.7, 99.5, 98.8, 99.9, and 96.5, respectively. All the samples were run in triplicate and the results were observed to be reproducible.