Development and validation of spectrophotometric and ion pair chromatographic techniques for estimation of telmisartan and hydrochlorothiazide

Ultraviolet spectrophotometric and ion pair chromatographic methods have been developed for simultaneous estimation of telmisartan and hydrochlrothiazide from their tablet dosage form. The first method involves multiwavelength spectrophotometric estimation (Method 1) where interference due to hydrochlrothiazide at 286 nm (wavelength for estimation of telmisartan) was eliminated by recording absorbance difference at 286 nm and 308 nm whereas interference of telmisartan at 262 nm (wavelength for estimation of hydrochlrothiazide) was removed by recording absorbance difference at 262 nm and 282 nm. Linearity of the response was demonstrated by telmisartan in the concentration range of 5-35 μg/ml with a square correlation coefficient (r2) of 0.9995. Linearity of the response was demonstrated by hydrochlrothiazide in the concentration range of 3-21 μg/ml with a square correlation coefficient (r2) of 0.9992. The second method utilizes ion pair chromatography (Method 2) on a HIQ sil ODS column (250 mm length x 4.6 mm internal diameter) using methanol: 0.0025 M orthophosphoric acid (70:30 by volume pH 4.6) containing 0.1% 1-hexane sulphonic acid monohydrate sodium salt as mobile phase with UV detection at 259 nm over a concentration range of 20-120 μg/ml for telmisartan and 12.5-75 μg/ml for hydrochlrothiazide. Losartan potassium was used as the internal standard. Both the methods were applied successfully for the analysis of the two drugs from their tablet dosage form. The results of analysis were validated statistically and as per ICHQ2B guidelines. The developed methods are simple, selective and reproducible and can be applied for routine analysis of formulations containing telmisartan and hydrochlrothiazide

DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC AND ION PAIR CHROMATOGRAPHIC TECHNIQUE FOR ESTIMATION OF VALSARTAN AND HYDROCHLOROTHIAZIDE

Two new simple, sensitive, rapid, accurate and reproducible methods (UV-spectrophotometric and ion pair chromatography) have been developed for simultaneous estimation of valsartan (VAL) and hydrochlrothiazide (HCTZ) from their tablet dosage form. The first method involves multiwavelength spectrophotometric method (Method 1) in which interference of HCTZ at 245nm (wavelength for estimation of VAL) was removed by recording absorbance difference at 245nm and 301 nm whereas HCTZ was estimated directly from its absorbance at 316 nm at which VAL shows no absorbance. Linearity of the response was demonstrated by VAL in the concentration range of 5-45 g/ml with a square correlation coefficient (r2) of 0.9998. Linearity of the response was demonstrated by HCTZ in the concentration range of 2-18 g/ml with a square correlation coefficient (r2) of 0.9994. The second method utilizes ion pair chromatography (Method 2) on a HIQ sil ODS column (250 mm* 4.6 mm i.d.) using methanol: 0.0025 M orthophosphoric acid: (70:30 by volume) having pH 4.6: 0.1% hexane sulphonic acid as mobile phase with UV detection at 259nm over concentration range for VAL is 240-0 μg/ml, and for HCTZ is 75-0μg/ml. Losartan potassium was used as the internal standard. The suggested procedures were checked using laboratory prepared mixtures and were applied successfully for the analysis of their tablet dosage form. The results of analysis were statistically analysed. Both the methods were validated as per ICH Q2B guideline

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation

Development and molecular modeling of Co(II), Ni(II) and Cu(II) complexes as high acting anti breast cancer agents

A series of cobalt, nickel and copper complexes of bidentate Schiff base derived from the condensation reaction of 4-amino-5-mercapto-3-methyl-1,2,4-triazole with 2-nitrobenzaldehyde had been synthesized. The synthesized Schiff base and their metal complexes have been characterized with the support of more than a few physicochemical techniques, elemental evaluation, magnetic moment measurements, spectroscopic, thermo gravimetric techniques and X-ray powder diffraction. Spectral analysis exhibits square planer geometry for Cu(II) complex while octahedral geometry for Co(II) and Ni(II) complexes. The Schiff base and their complexes have been screened for their anticancer activity using MCF7 cell line. In molecular docking learn exhibits that Ni(II) complex is more active confirmed quantity of interaction in particular hydrogen bond interaction with ASN142 and charge interactions with ASP97 and GLU99

Abundance, viability and diversity of the indigenous microbial populations at different depths of the NEEM Greenland ice core

The 2537-m-deep North Greenland Eemian Ice Drilling (NEEM) core provided a first-time opportunity to perform extensive microbiological analyses on selected, recently drilled ice core samples representing different depths, ages, ice structures, deposition climates and ionic compositions. Here, we applied cultivation, small subunit (SSU) rRNA gene clone library construction and Illumina next-generation sequencing (NGS) targeting the V4–V5 region, to examine the microbial abundance, viability and diversity in five decontaminated NEEM samples from selected depths (101.2, 633.05, 643.5, 1729.75 and 2051.5 m) deposited 300–80 000 years ago. These comparisons of the indigenous glacial microbial populations in the ice samples detected significant spatial and temporal variations. Major findings include: (a) different phylogenetic diversity of isolates, dominated by Actinobacteria and fungi, compared to the culture-independent diversity, in which Proteobacteria and Firmicutes were more frequent; (b) cultivation of a novel alphaproteobacterium; (c) dominance of Cyanobacteria among the SSU rRNA gene clones from the 1729.75-m ice; (d) identification of Archaea by NGS that are rarely detected in glacial ice; (e) detection of one or two dominant but different genera among the NGS sequences from each sample; (f) finding dominance of Planococcaceae over Bacillaceae among Firmicutes in the brittle and the 2051.5-m ice. The overall beta diversity between the studied ice core samples examined at the phylum/class level for each approach showed that the population structure of the brittle ice was significantly different from the two deep clathrated ice samples and the shallow ice core