Characterization of the in vitro metabolic profile of nazartinib in HLMs using UPLC-MS/MS method: In silico metabolic lability and DEREK structural alerts screening using StarDrop software.

The orally given, irreversible, third-generation inhibitor of the epidermal growth factor receptor (EGFR), known as Nazartinib (EGF816), is now undergoing investigation in Phase II clinical trials conducted by Novartis for Non-Small Cell Lung Cancer. The primary aim of the current research was to establish a rapid, specific, environmentally friendly, and highly versatile UPLC-MS/MS methodology for the determination of nazartinib (NZT) levels in human liver microsomes (HLMs). Subsequently, same approach was used to examine the metabolic stability of NZT. The UPLC-MS/MS method employed in HLMs was validated as stated in the bioanalytical method validation criteria outlined by the US- FDA. The evaluation of the metabolic stability of NZT and the identification of potentially structural alarms were performed using the StarDrop software package that includes the P450 and DEREK software. The calibration curve for NZT showed a linearity in the range from 1 to 3000 ng/mL. The inter-day accuracy and precision exhibited a range of values between -4.33 % and 4.43 %, whereas the intra-day accuracy and precision shown a range of values between -2.78 % and 7.10 %. The sensitivity of the developed approach was verified through the determination of a LLOQ of 0.39 ng/mL. The intrinsic clearance and in vitro half-life of NZT were assessed to be 46.48 mL/min/kg and 17.44 min, respectively. In our preceding inquiry, we have effectively discerned the bioactivation center, denoted by the carbon atom between the unsaturated conjugated system and aliphatic linear tertiary amine. In the context of computational software, making minor adjustments or substituting the dimethylamino-butenoyl moiety throughout the drug design process may increase the metabolic stability and safety properties of new synthesized derivatives. The efficiency of utilizing different in silico software approaches to conserve resources and reduce effort was proved by the outcomes attained from in vitro incubation experiments and the use of NZT in silico software.

An ultra-fast green ultra-high-performance liquid chromatography-tandem mass spectrometry method for estimating the in vitro metabolic stability of zotizalkib in human liver microsomes.

Zotizalkib (ZTK, TPX-0131) is a fourth-generation highly effective inhibitor of wild-type anaplastic lymphoma kinase (ALK) and ALK-resistant mutations that can penetrate the central nervous system. It exhibited greater potency compared to all five officially approved ALK inhibitors. The aim of this study was to develop a rapid, accurate, eco-friendly, and highly sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for measuring the concentration of ZTK in human liver microsomes (HLMs). The validation aspects of the current UHPLC-MS/MS methodology in the HLMs were conducted in accordance with the bioanalytical method validation standards specified by the US Food and Drug Administration. ZTK and encorafenib were separated using an Agilent C8 column (Eclipse Plus) and an isocratic mobile phase. The calibration curve for the developed ZTK exhibited a linear relationship within the concentration range of 1-3000 ng/mL. The results from the Analytical Green-ness Metric Approach program (0.76) suggested that the created method demonstrated a significant degree of environmental sustainability. The in vitro half-life (t1/2) and intrinsic clearance (Clint) of ZTK were determined to be 15.79 min and 51.35 mL/min/kg, respectively that suggests the ZTK exhibits characteristics similar to those of a medication with a high extraction ratio. These approaches are crucial for the progress of novel pharmaceutical development, especially in improving metabolic stability.

An ultra-fast ultra-high-performance liquid chromatography-tandem mass spectrometry method for estimating the in vitro metabolic stability of palbociclib in human liver microsomes: In silico study for metabolic lability, absorption, distribution, metabolism, and excretion features, and DEREK alerts screening.

Palbociclib (Ibrance; Pfizer) was approved for the management of metastatic breast cancer characterized by hormone receptor-positive/human epidermal growth factor receptor 2 negative status. The objective of this study was to create a fast, precise, environmentally friendly, and highly sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry approach for quantifying palbociclib (PAB) in human liver microsomes with the application for assessing metabolic stability. The validation features were performed in agreement with the bioanalytical method validation standards outlined by the US Food and Drug Administration. The StarDrop software (WhichP450 and DEREK modules) was used in screening the metabolic lability and structural alerts of PAB. The separation of PAB and encorafenib (as an internal standard) was achieved on a C8 column, employing an isocratic mobile phase. The inter-day and intra-day accuracy and precision ranged from -6.00% to 4.64% and from -2.33% to 3.13%, respectively. The constructed calibration curve displayed a linearity in the range of 1-3000 ng/mL. The sensitivity of the established approach was proven by the lower limit of quantification of 0.73 ng/mL. The Analytical GREEness calculator results revealed the high level of greenness of the developed method. The PAB's metabolic stability (t1/2 of 18.5 min and a moderate clearance (Clint) of 44.8 mL/min/kg) suggests a high extraction ratio medication that matched the WhichP450 software results.

Short-term air pollution and greenness exposures on oxidative stress in urban and peri-urban residents in Beijing: A part of AIRLESS study.

BACKGROUND: Exposure to air pollution has been associated with increased risks of cardiopulmonary diseases, cancer, and mortality, whereas residing near green spaces may reduce the risks. However, limited research explores their combined effect on oxidative stress. METHODS: A total of 251 participants with multi-time measurements were included in the longitudinal-designed study. Personal gaseous air pollutants (CO, NO, NO2, and O3,) and particulate pollution (PM1, PM2.5, and PM10) were measured and followed in two 7-day windows while ambient exposure levels and urine samples were collected simultaneously. Participants' Normalized Difference Vegetation Index (NDVI) was estimated and used to represent greenness exposure. Urinary oxidative stress biomarkers include free malondialdehyde (MDA), total MDA, and 8-hydroxydeoxyguanosine (8-OHdG). Linear mixed-effects models were used to independently and jointly estimate the associations of greenness and air pollution with oxidative stress biomarkers. RESULTS: We found consistent positive associations of personal ozone (O3) exposure with 8-OHdG percent changes, and this association was modified by gender and outdoor activity frequency. Consistent positive associations of personal lag 2-day carbon monoxide (CO) exposure with the percent changes of the three oxidative stress biomarkers were significant. We additionally observed that individuals who lived in greener areas had lower levels of urinary-free and total MDA. Participants in the highest NDVI tertile had 0.38 and 0.46 lower free and total MDA levels, [95 % CI: (-0.70, -0.05) and (-0.78, -0.13)], compared to the lowest NDVI tertile. There was also evidence indicating the modification effects by area, education, and outdoor activity frequency on associations between NDVI exposure and creatinine adjusted free MDA (all Pfor interaction < 0.05). Additional greenness modification effects on personal O3 exposure with urinary 8-OHdG was observed. CONCLUSION: Our study provides biological evidence of the modification effect of the built environment on the impact of air pollution.

Ultra-fast UPLC-MS/MS approach for estimating X-376 in human liver microsomes: Evaluation of metabolic stability via in silico software and in vitro analysis.

X-376 is a novel anaplastic lymphoma kinase (ALK) inhibitor that is capable of penetrating the blood brain barrier. This makes it suitable for use in patients with ALK-positive non-small cell lung cancer (NSCLC) who have metastases in the central nervous system. This study developed a highly sensitive, fast, eco-friendly, and reliable UPLC-MS/MS approach to quantify X-376 in human liver microsomes (HLMs). This approach was used to evaluate X-376's metabolic stability in HLMs in vitro. The UPLC-MS/MS analytical technique validation followed US-FDA bio-analytical method validation guidelines. StarDrop software, containing P450 metabolic and DEREK modules, was utilized to scan X-376's chemical structure for metabolic lability and hazardous warnings. X-376 and Encorafenib (ENF as internal standard) were resoluted on the Eclipse Plus C18 column utilizing an isocratic mobile phase method. The X-376 calibration curve was linear from 1 to 3000 ng/mL. The precision and accuracy of this study's UPLC-MS/MS approach were tested for intra- and inter-day measurements. Inter-day accuracy was -1.32% to 9.36% while intra-day accuracy was -1.5% to 10.00%. The intrinsic clearance (Clint) and in vitro half-life (t1/2) of X-376 were 59.77 mL/min/kg and 13.56 min. The high extraction ratio of X-376 supports the 50 mg twice-daily dose for ALK-positive NSCLC and CNS metastases patients. In silico software suggests that simple structural changes to the piperazine ring or group substitution in drug design may improve metabolic stability and safety compared to X-376.

The effect of residential greenness on cardiovascular mortality from a large cohort in South China: An in-depth analysis of effect modification by multiple demographic and lifestyle characteristics.

BACKGROUND: The potential for residential greenness to improve cardiovascular health through both physical and psychological mechanisms is well recognized. However, evidence from rapidly urbanizing developing countries and cohort-based causal inference approaches, remains limited. We aim to examine the effect of residential greenness and time to cardiovascular mortality in South China. METHODS: We utilized data from a community-based population survey involving 748,209 participants at baseline from 2009 to 2015, followed up until 2020. Residential greenness exposure was assessed by the annual Normalized Difference Vegetation Index (NDVI) in the 500 m radius of each participant's residence. We used time-varying proportional hazard Cox models coupled with inverse probability weighting to fit marginal structural models and obtain hazard ratios (HRs) for cardiovascular disease (CVD) mortality after adjusting for confounders. Multiple effect modifiers on both additive and multiplicative scales were further explored. RESULTS: A total of 15,139 CVD-related deaths were identified during a median of 7.9 years of follow-up. A protective effect was found between higher greenness exposure and reduced CVD mortality, with a 9.3 % lower rate of total CVD mortality (HR 0.907, 95 % CI 0.859-0.957) based on a 0.1 increase in annual average NDVI. Demographic (age, marital status) and lifestyle factors (smoking, drinking status) were found to modify the association between residential greenness and CVD mortality (all P interaction values < 0.05 or 95 %CI for RERI excluded the value 0). Notably, this effect was more pronounced among older adults, married, and individuals having healthier lifestyles, indicating a greater benefit from greenness for these subgroups. CONCLUSIONS: Our findings support a causal link between increased residential greenness exposure and a reduced risk of CVD mortality in South China with marked heterogenous effects, which has public health implications for cultivating greener urban environments to mitigate the impact of CVD within the context of rapid urbanization.

Design, Characterization and Biopharmaceutical Applications of Novel Green Boron-Carbon Quantum Dots for Quantification of Apalutamide; Greenness Evaluations.

The diagnosis of prostate cancer has been evolving in the current decade, with expected mortality rates of 499,000 death by the year 2030. Apalutamide (APL) has been approved in 2018 as the first drug for the controlling of prostate cancer. APL significant success warrantied its high global sales, which are expected to surpass 58% of segment market sales (together with another drug; enzalutamide). Therefore, new, fast and environmentally friendly analytical methods are required for its determination for the quality control and biological monitoring purposes. The proposed research designs and evaluates the first fluorimetric approach based on novel porous green boron-doped carbon quantum dots (B@CDs) for the determination of APL in biopharmaceutical matrices. The synthetic approach has high quantum yield (31.15%). B@CDs were characterized using several tools, including transmission electron microscopy (TEM), dynamic light scattering (DLS), FTIR and Energy dispersive X-ray spectroscopy (EDX) which proved their improved surface properties with an average nano-diameter of 3.0 nm. The interaction between B@CDs and APL led to enhancement their fluorescence at 441 nm (excitation at 372 nm). The approach was validated for the determination of APL within concentration range of 15.0-700.0 ng mL- 1 with quantification limit LOQ 4.37 ng mL- 1 and detection limit LOD 1.44 ng mL- 1. The approach was successfully applied for the determination of APL in human plasma and pharmaceutical monitoring of its marketed tablet form. Then, the approach was assessed for its environmental impact using different metrics and proved its ecological greenness.

ChlorTox scale assessment, greenness, and whiteness evaluation of selective spectrophotometric analysis of dimenhydrinate and cinnarizine.

Nausea and vomiting are considered common series side effects induced by chemotherapy treatment in cancer patients. This annoying side effect can impair the patient's compliance to cancer treatment and affect their quality of life. Dimenhydrinate and cinnarizine in combined pharmaceutical dosage form is used to control chemotherapy induced nausea and vomiting in cancer patients. For safety, selective spectrophotometric methods based on novel dual resolution strategies were introduced to estimate dimenhydrinate and cinnarizine in presence of their harmful impurities namely benzophenone and 1- (diphenylmethyl)piperazine, respectively. These methods namely, dual ratio difference (DRD), dual ratio extraction (DRE) and dual absorbance extraction coupled with dual ratio extraction (DAE-DRE) were successfully performed to simultaneously analyze the drug of interests dimenhydrinate and cinnarizine in their pure form, synthetic mixtures and in market dosage form. Linearity ranges were 6.0-60.0 µg/mL and 3.0-30.0 µg/mL for dimenhydrinate and cinnarizine, respectively with good recovery% of Mean ± SD for all the proposed methods 99.82 ± 0.48, 99.79 ± 0.40, 100.14 ± 0.82, 100.03 ± 0.69, respectively. ICH guidelines were adhered in accordance with confirming validation of the proposed methods where fulfilling results were accomplished. Various unified greenness and whiteness assessment tools, such as the chlorTox scale, greenness index via spider chart, AGREE (The Analytical Greenness Metric), green certificate, and the RGB12 algorithm were employed in this research to assess the greenness and sustainability of the introduced UV-spectrophotometric methods in comparison to the reported HPLC method. As a result, these methods hold significant potential for utilization in the quality control department of pharmaceutical companies, contributing to enhanced pharmaceutical product analysis and overall sustainability practices.

Greenness, air pollution, and mortality risk: a retrospective cohort study of patients with lung cancer in China.

The association between long-term exposure to air pollution and mortality from lung cancer has been established, yet evaluations of the potential mitigating effects of greenness on this impact are scarce. We conducted a cohort study in Pingyi County. A two-level Cox proportional hazards regression model was used to examine the associations among long-term exposure to air pollution, residential greenness, and lung cancer mortality. Among the examined pollutants, nitrogen dioxide exhibited the most significant adverse effects and highest risk of lung cancer mortality, with hazard ratio (HR) = 2.783 (95% confidence interval [CI]: 1.885-4.107) for all-cause mortality, HR = 2.492 (95%CI: 1.659-3.741) for tumour-related mortality, and HR = 2.431 (95%CI: 1.606-3.678) for lung cancer mortality. Higher greenness values were associated with a reduced risk of lung cancer mortality. These findings suggest the importance of implementing strategies for increasing greenness to reduce the health impacts of air pollution.

A highly sensitive first derivative synchronous spectrofluorimetric approach for the simultaneous analysis of the anti-breast cancer co-administered drugs, letrozole and tramadol in dosage forms and human plasma at nanogram levels.

Letrozole is an anticancer medication prescribed for the management of estrogen receptor-positive breast cancer in postmenopausal women. Chronic pain is prevalent in patients receiving chemotherapy, leading to the use of adjuvant analgesics such as tramadol. This work introduces the first analytical approach for the concurrent quantification of letrozole and tramadol, two co-administered drugs, employing a rapid, highly sensitive, eco-friendly, and cost-effective first derivative synchronous spectrofluorimetric technique. The fluorescence of tramadol and letrozole was measured at wavelengths of 235.9 nm and 241.9 nm, respectively using a wavelength difference (Δλ) of 60.0 nm. The developed approach demonstrated exceptional linearity (r ˃ 0.999) within the specified concentration ranges for tramadol (10.0-1200.0 ng/mL) and letrozole (1.0-140.0 ng/mL). The results demonstrated that the proposed technique exhibits a high level of sensitivity, with detection limits of 0.569 and 0.143 ng/mL for tramadol and letrozole, respectively, indicating the good bioanalytical applicability. The within-run precisions, both intra-day and inter-day, for both analytes, were less than 0.71 % RSD. The developed approach was effectively applied to simultaneously estimate the mentioned drugs in their tablets and human plasma samples, achieving high percentage recoveries and low % RSD values. In order to assess the environmental sustainability of the developed approach, Analytical GREEnnessNNESS (AGREE) and the Green Analytical Procedure Index (GAPI) metric tools were employed. Both tools revealed that the developed approach is excellent green, suggesting its usage as an environmentally-friendly alternative for the routine assayof the investigated pharmaceuticals. The developed approach was validated according to the ICHQ2 (R1) requirements.

An eco-friendly and cost-effective HPTLC method for quantification of COVID-19 antiviral drug and co-administered medications in spiked human plasma.

The coronavirus-2 has led to a global pandemic of COVID-19 with an outbreak of severe acute respiratory syndrome leading to worldwide quarantine measures and a rise in death rates. The objective of this study is to propose a green, sensitive, and selective densitometric method to simultaneously quantify remdesivir (REM) in the presence of the co-administered drug linezolid (LNZ) and rivaroxaban (RIV) in spiked human plasma. TLC silica gel aluminum plates 60 F254 were used as the stationary phase, and the mobile phase was composed of dichloromethane (DCM): acetone (8.5:1.5, v/v) with densitometric detection at 254 nm. Well-resolved peaks have been observed with retardation factors (Rf) of 0.23, 0.53, and 0.72 for REM, LNZ, and RIV, respectively. A validation study was conducted according to ICH Q2 (R1) Guidelines. The method was rectilinear over the concentration ranges of 0.2-5.5 µg/band, 0.2-4.5 µg/band and 0.1-3.0 µg/band for REM, LNZ and RIV, respectively. The sensitivities of REM, LIN, and RIV were outstanding, with quantitation limits of 128.8, 50.5, and 55.8 ng/band, respectively. The approach has shown outstanding recoveries ranging from 98.3 to 101.2% when applied to pharmaceutical formulations and spiked human plasma. The method's greenness was assessed using Analytical Eco-scale, GAPI, and AGREE metrics.

Isoquinoline-based intrinsic fluorescence assessment of erythropoiesis-stimulating agent, Roxadustat (FG-4592), in tablets: applications to content uniformity and human plasma evaluation.

In the present study, a first validated and green spectrofluorimetric approach for its assessment and evaluation in different matrices was investigated. After using an excitation wavelength of 345 nm, Roxadustat (ROX) demonstrates a highly native fluorescence at an emission of 410 nm. The influences of experimental factors such as pH, diluting solvents, and different organized media were tested, and the most appropriate solvent choice was ethanol. It was confirmed that there was a linear relationship between the concentration of ROX and the relative fluorescence intensity in the range 60.0-1000.0 ng ml-1, with the limit of detection and limit of quantitation, respectively, being 17.0 and 53.0 ng ml-1. The mean recoveries % [±standard deviation (SD), n = 5] for pharmaceutical preparations were 100.11% ± 2.24%, whereas for plasma samples, they were 100.08 ± 1.08% (±SD, n = 5). The results obtained after the application of four greenness criteria, Analytical Eco-Scale metric, NEMI, GAPI, and AGREE metric, confirmed its eco-friendliness. In addition, the whiteness meter (RGB12) confirmed its level of sustainability. The International Council for Harmonisation (ICH) criteria were used to verify the developed method through the study in both spiked plasma samples and content uniformity evaluation. An appropriate standard for various applications in industry and quality control laboratories was developed.

Integration of a facile sustainable resonance Rayleigh scattering switchable-based system for feasible determination of centrophenoxine, a nootropic and antioxidant agent; application to crude materials and dosage forms.

The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15-47 ng mL-1, whereas the linearity was assessed to be in the range of 50-2000 ng mL-1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field.

White analytical insight for sensitive fluorescent determination of semaglutide and tirzepatide in pharmaceuticals and biological matrices.

The present study is focused on the sensitive determination of newly FDA-approved glucagon-like-peptide agonists semaglutide (SEM) and tirzepatide (TIR). Direct, selective and label-free spectrofluorometric method was proposed and validated (according to ICH guidelines) for determination SEM and TIR in their pure form, newly approved pharmaceuticals and spiked human plasma. The developed method was based on measuring the native fluorescence of SEM and TIR in ethanol at 294.8 and 303 nm after being excited at 216 and 225 nm for SEM and TIR in order. The method sensibility allowed the quantification of both drugs in nano-scale up to 10 ng/mL. Several experimental variables including solvent type, surfactant, and pH were optimized after several attempts to get the best sensitivity for both drugs. The mean recovery percentage of SEM was compared and found in agreement with the reported method using student's t-test and the variance ratio F-test. Additionally, the greenness and whiteness profiles for this approach were evaluated using the GAPI, AGREE, and RGB algorithm; the positive results supported its use as great candidates for successful implementation in quality control labs and the pharmaceutical analysis companies.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Determination of Fe, Cu, and Pb in edible oils using choline chloride:ethylene glycol deep eutectic solvent-based dispersive liquid-liquid microextraction associated with microwave-induced plasma optical emission spectrometry.

A new simple, fast and environmentally friendly deep eutectic solvent based dispersive liquid-liquid microextraction (DES-based DLLME) methodology assisted by vortex is presented for the separation and preconcentration of three elements (i.e., Fe, Cu and Pb) from edible oil samples (i.e., soybean, sunflower, rapeseed, sesame, and olive oil) prior to the determination by microwave-induced plasma optical emission spectrometry (MIP-OES). The deep eutectic solvent selected as extractant (i.e., choline chloride and ethylene glycol, 1:2) is synthesized and characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H NMR) and differential scanning calorimetry (DSC), and the extraction conditions are optimized by a two steps experimental design. Under the optimum extraction conditions (i.e., diluted sample weight: 8.6 g; DES volume: 100 µL; extraction time: 1 min; centrifugation time and speed: 3 min and 3000 rpm; and dispersion system: vortex) the analytical method presents excellent linearity (i.e., R2 values higher than 0.99) in the range 10-500 µg kg-1, repeatability (i.e., CV values lower than 9.2%), and limits of detection (LOD) values of 3, 2 and 0.7 µg kg-1 for Pb, Fe and Cu, respectively. None of the analytes displayed amounts over the upper limit permitted by law, and recovery values of all analytes evaluated in the different samples using external standard calibration were close to 100%, which excludes significant matrix effects. Finally, AGREEprep metric has been used to evaluate the method greenness (final score of 0.47) and it has been compared successfully with previous publications for the same type of analytes and matrices.

Design of Experimental Approach for Development of Rapid High Performance Liquid Chromatographic Process for Simultaneous Estimation of Metoprolol, Telmisartan, and Amlodipine from Formulation: Greenness and Whiteness Evaluation.

The design of an experimental approach, the Box-Behnken design, was implemented to optimize the chromatographic condition to develop a rapid HPLC procedure for quantification of a ternary mixture of metoprolol (MET), telmisartan (TEL), and amlodipine (AML) from the formulation. The perturbation plots, contour, and 3D response surface pictures were developed to study the impact of each variable on the analytes' retention time and the probable interaction between the parameters with fewer chromatographic runs. The optimized HPLC method separated the three analytes within 5 min with excellent selectivity and peak shape on a Zorbax C18 HPLC column using acetonitrile and phosphate buffer (20 mM, pH 5.8) with isocratic elution at a 1.1 mL/min flowrate. A wavelength 230 nm was utilized to monitor the elute. The validation of proposed method demonstrated a wide linearity range of 10-200 µg/mL for MET and TEL and 5-50 µg/mL for AML along with an excellent correlation coefficient. The correctness of the HPLC approach was further confirmed by excellent recovery of the added amount of analytes utilizing the standard addition technique. The recommended HPLC approach was employed safely for quality assurance of the formulation, because the evaluation of the method's greenness and whiteness confirmed the environmentally friendly nature of the approach.

Residential greenness and lower breast and prostate cancer incidence: Evidence from a retrospective cohort study of 977,644 participants from Israel.

BACKGROUND: There is limited evidence on the associations between residential greenness and cancer incidence in longitudinal studies. OBJECTIVES: The aim of the study was to evaluate the associations between weighted mean residential greenness exposure and cancer incidence. METHODS: This is a registry based retrospective cohort study of 977,644 participants. The residential greenness exposure was estimated for every participant, as the weighted mean residential greenness exposure. This was based on the mean Normalized Difference Vegetation Index (NDVI) in the residential small geographic area and the duration of the residence in this area. Cancer incidence cases included consecutive newly diagnosed cases of primary cancer. Analyses were conducted for all cancer sites, lung cancer, bladder cancer, breast cancer, prostate cancer and melanoma-skin cancer. Cox regression models were used to evaluate the crude and adjusted associations (hazards ratios (HR) and its 95 % confidence intervals (CIs)) between tertiles of residential greenness and cancer incidence. Further adjusted models to nitrogen oxides (NOx) were estimated. RESULTS: After adjustment to covariates, exposure to the highest tertile of residential greenness, compared to the lowest, were associated with lower risk for all cancer sites (HR = 0.88, 95 % CI: 0.86-0.90), breast cancer (HR = 0.85, 95 % CI: 0.80-0.89) and prostate cancer (HR = 0.85, 95 % CI: 0.79-0.91). In addition, lower risk were observed for the middle tertile of exposure and all cancer sites (HR = 0.88, 95 % CI: 0.86-0.90), breast cancer (HR = 0.88, 95 % CI: 0.84-0.92) and prostate cancer (HR = 0.83, 95 % CI: 0.79-0.89). There was no evidence for mediation by air pollution (NOx). DISCUSSION: Residential greenness demonstrated beneficial associations with lower risk for all cancers, breast and prostate cancers. If our observations will be replicated, it may present a useful avenue for public-health intervention to reduce cancer burden through the provision of greenness exposure.

The built environment and cancer survivorship: A scoping review.

BACKGROUND: There are more than 32 million cancer survivors worldwide. The built environment is one of the contextual factors that may influence cancer survivorship. However, studies investigating the interdisciplinary field of the built environment and cancer survivorship are lacking. OBJECTIVE: To conduct a systematic review of the existing literature regarding the relationship between the built environment and cancer survivorship, identify any knowledge gaps, and recommend future research directions. METHODS: A systematic literature search was performed by searching OVID Medline, Embase, CINAHL, and Web of Science Core Collection. RESULTS: Of 4235 unique records identified, 26 studies met eligibility criteria. Neighborhood walkability and greenness were the most examined built environment characteristics among the included studies. Walkability was found to be associated with various cancer survivorship experience, including increased levels of physical activity, lowered body mass index, and improved quality of life. The association between greenness and cancer survivorship outcomes were inconsistent across the included studies. Additionally, studies have reported the relationship between light and noise pollution and sleep among cancer survivors. Regarding blue space, in one qualitative study, breast cancer survivors brought up the healing properties of water. CONCLUSION: Our scoping review demonstrated a breadth of current cancer survivorship research in the field of neighborhood walkability and greenness, but fewer studies detailing other aspects of the built environment as defined by this review, such as light pollution, noise pollution, and blue space. We identified future research directions for those interested in this interdisciplinary field, which can provide insights for urban planners and policy makers on how to best leverage the built environment to promote the health and wellbeing of cancer survivors.

Potential causal links and mediation pathway between urban greenness and lung cancer mortality: Result from a large cohort (2009 to 2020).

Urban greenness, as a vital component of the urban environment, plays a critical role in mitigating the adverse effects of rapid urbanization and supporting urban sustainability. However, the causal links between urban greenness and lung cancer mortality and its potential causal pathway remain poorly understood. Based on a prospective community-based cohort with 581,785 adult participants in southern China, we applied a doubly robust Cox proportional hazard model to estimate the causal associations between urban greenness exposure and lung cancer mortality. A general multiple mediation analysis method was utilized to further assess the potential mediating roles of various factors including particulate matter (PM1, PM2.5-1, and PM10-2.5), temperature, physical activity, and body mass index (BMI). We observed that each interquartile range (IQR: 0.06) increment in greenness exposure was inversely associated with lung cancer mortality, with a hazard ratio (HR) of 0.89 (95 % CI: 0.83, 0.96). The relationship between greenness and lung cancer mortality might be partially mediated by particulate matter, temperature, and physical activity, yielding a total indirect effect of 0.826 (95 % CI: 0.769, 0.887) for each IQR increase in greenness exposure. Notably, the protective effect of greenness against lung cancer mortality could be achieved primarily by reducing the particulate matter concentration.