Linear solvent strength model on porous graphitic carbon stationary phase using high temperature liquid chromatographic method for allopurinol related substances analysis.

A high-performance liquid chromatography (HPLC) method was developed for the analysis of Allopurinol and its Ph.Eur. impurities using a porous graphitic carbon (PGC) stationary phase. Retention behavior of solutes was studied across a wide temperature range (30-90 °C) and various gradient times (5-20 min). Analysis of the data revealed distinct retention mechanisms between reversed-phase and PGC phases. However, it was proved that the retention of Allopurinol and its Ph.Eur. impurities on PGC stationary phase can be effectively modeled using the linear solvent strength (LSS) theory. This allows for the utilization of LSS-based method development software to optimize methods under these conditions. By using commercial chromatographic modeling software, separation of Allopurinol and Ph.Eur. impurities was optimized within a large design space. At the optimized operating conditions (pH = 2.0, tG = 6 min, T = 60 °C), all solutes were separated within 6 min with baseline resolution. Comparison between predicted and experimentally measured chromatograms further confirmed the applicability of LSS theory in developing analytical methods for PGC-based HPLC systems. The presented approach offers a general framework for method development on PGC phases.

Effect of time-invariant pressure gradients on peak formation and efficiency in ultrahigh-pressure liquid chromatography.

In chromatography, pressure can affect the retention factors of compounds significantly. In liquid chromatography, this effect is primarily related to the change in the molecular volume of solute during adsorption that is remarkably high for large biomolecules such as peptides and proteins. As a result, the migration velocities of chromatographic bands vary spatially through the column affecting the degree of band broadening. In this work, based on theoretical considerations, chromatographic efficiencies are studied under pressure-induced gradient conditions. The retention factor and migration velocity of different components are examined, and it is shown that components with the same retention time can have different migration patterns. The width of the initial band after injection is affected by the pressure gradient, providing significantly thinner initial bands for compounds with higher pressure sensitivity. In addition to classical band broadening phenomena, the influence of pressure gradients on band broadening is remarkable. The positive velocity gradient leads to extra band broadening. Our results clearly demonstrate that the zones are significantly wider at the end of the column if the change of molar volume of solute during adsorption is large. If the pressure drop is increasing, this effect becomes more significant. In the same time, the high release velocity of the bands somewhat counteracts the extra band broadening effect, however, it can not offset it perfectly. As a result, the separation efficiency of large biomolecules is decreased significantly due to the chromatographic pressure gradient. Under UHPLC conditions, the extent of apparent efficiency loss can reach up to 50% compared to the intrinsic efficiency of the column.

The Effectiveness of Supplementation with Key Vitamins, Minerals, Antioxidants and Specific Nutritional Supplements in COPD-A Review.

Currently, an increasing amount of evidence supports the notion that vitamins C, D and E, carotenoids, and omega-3 fatty acids may protect against the progression of chronic respiratory diseases. Although chronic obstructive pulmonary disease (COPD) primarily affects the lung, it is often accompanied by extrapulmonary manifestations such as weight loss and malnutrition, skeletal muscle dysfunction, and an excess of harmful oxidants, which can lead to a decline in quality of life and possible death. Recently, the role of various vitamins, minerals, and antioxidants in mitigating the effects of environmental pollution and smoking has received significant attention. Therefore, this review evaluates the most relevant and up-to-date evidence on this topic. We conducted a literature review between 15 May 2018 and 15 May 2023, using the electronic database PubMed. Our search keywords included COPD, chronic obstructive pulmonary disease, FEV1, supplementation: vitamin A, vitamin D, vitamin E, vitamin C, vitamin B, omega-3, minerals, antioxidants, specific nutrient supplementations, clinical trials, and randomized controlled trials (RCTs). We focused on studies that measured the serum levels of vitamins, as these are a more objective measure than patient self-reports. Our findings suggest that the role of appropriate dietary supplements needs to be reconsidered for individuals who are predisposed to or at risk of these conditions.

Significant Regional Differences in Lung Cancer Incidence in Hungary: Epidemiological Study Between 2011 and 2016.

Objective: Hungary has one of the highest incidences and mortality rates of lung cancer (LC), therefore the objective of this study was to analyse and compare LC incidence and mortality rates between the main Hungarian regions. Methods: This nationwide, retrospective study used data from the National Health Insurance Fund and included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between Jan 1, 2011 and Dec 31, 2016. Age-standardized incidence and mortality rates were calculated and compared for the main regions. Results: The highest incidence rate in males was recorded in Northern Hungary (146.8/100,000 person-years [PY]), while the lowest rate was found in Western Transdanubia (94.7/100,000 PY in 2011). All rates showed a declining trend between 2011 and 2016, with the largest decrease in the Northern Great Plain (-20.0%; p = 0.008). LC incidence and mortality rates in women both showed a rising tendency in all regions of Hungary, reaching the highest in Central Hungary (59.86/100,000 PY in 2016). Lung cancer incidence and mortality rates in males correlated with the level of education and smoking prevalence (p = 0.006 and p = 0.01, respectively) in the regions. A correlation with GDP per capita and Health Development Index (HDI) index could also be observed in the Hungarian regions, although these associations were not statistically significant. No correlations could be detected between these parameters among females. Conclusion: This analysis revealed considerable differences in the epidemiology of LC between the 7 main Hungarian regions. LC incidence and mortality rates significantly correlated with smoking and certain socioeconomic factors in men, but not in women. Further research is needed to explain the regional differences.

Age and Gender Specific Lung Cancer Incidence and Mortality in Hungary: Trends from 2011 Through 2016.

Objective: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database. Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between January 1, 2011 and December 31, 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any cancer treatment other than lung cancer protocols were excluded. Results: Lung cancer incidence and mortality increased with age, peaking in the 70-79 age group (375.0/100,000 person-years) among males, while at 60-69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46-3.01 (p < 0.0001) among the 70-79 age group. We found 2-11% decrease in male incidence rate at most age groups, while a significant 1-3% increase was observed in older females (>60) annually during the study period. Conclusion: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary decreased in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population.

Improvement in Lung Cancer Survival: 6-Year Trends of Overall Survival at Hungarian Patients Diagnosed in 2011-2016.

Objective: Lung cancer is one of the most common cancers worldwide and its survival is still poor. The objective of our study was to estimate long-term survival of Hungarian lung cancer patients at first time based on a nationwide review of the National Health Insurance Fund database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between January 1, 2011 and December 31, 2016. Survival rates were evaluated by year of diagnosis, patient gender and age, and morphology of lung cancer. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.7 and 65.9 years during study period. One- and 5-year overall survival rates for the total population were 42.2 and 17.9%, respectively. Survival was statistically associated with gender, age and type of lung cancer. Female patients (n = 16,362) had 23% better survival (HR: 0.77, 95% confidence interval (CI): 0.75-0.79; p < 0.001) than males (n = 25,492). The highest survival rates were found in the 20-49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.5%). We measured 5.3% improvement (9.2% adjusted) in lung cancer survival comparing the period 2015-2016 to 2011-2012 (HR: 0.95 95% CI: 0.92-0.97; p = 0.003), the highest at females <60 year (0.86 (adjusted HR was 0.79), interaction analysis was significant for age and histology types. Conclusion: Our study provided long-term Lung cancer survival data in Hungary for the first time. We found a 5.3% improvement in 5-year survival in 4 years. Women and young patients had better survival. Survival rates were comparable to-and at the higher end of-rates registered in other East-Central European countries (7.7%-15.7%).

Increase in the Length of Lung Cancer Patient Pathway Before First-Line Therapy: A 6-Year Nationwide Analysis From Hungary.

Objective: This study aimed to examine the characteristics of the lung cancer (LC) patient pathway in Hungary during a 6-years period. Methods: This nationwide, retrospective study included patients newly diagnosed with LC (ICD-10 C34) between January 1, 2011, and December 31, 2016, using data from the National Health Insurance Fund (NHIF) of Hungary. The following patient pathway intervals were examined: system, diagnostic and treatment interval by age, gender, tumor type, study year and first-line LC therapy. Results: During the 6-years study period, 17,386 patients had at least one type of imaging (X-ray or CT/MRI) prior to diagnosis, and 12,063 had records of both X-ray and CT/MRI. The median system interval was 64.5 days, and it was 5 days longer among women, than in men (68.0 vs. 63.0 days). The median system interval was significantly longer in patients with adenocarcinoma compared to those with squamous cell carcinoma or small cell lung cancer (70.4 vs. 64.0 vs. 48.0 days, respectively). Patients who received surgery as first-line treatment had significantly longer median system intervals compared to those receiving chemotherapy (81.4 vs. 62.0 days). The median system interval significantly increased from 62.0 to 66.0 days during the 6-years study period. Conclusion: The LC patient pathway significantly increased in Hungary over the 6-years study period. There were no significant differences in the length of the whole LC patient pathway according to age, however, female sex, surgery as first-line treatment, and adenocarcinoma were associated with longer system intervals.

Revising Incidence and Mortality of Lung Cancer in Central Europe: An Epidemiology Review From Hungary.

Objective: While Hungary is often reported to have the highest incidence and mortality rates of lung cancer, until 2018 no nationwide epidemiology study was conducted to confirm these trends. The objective of this study was to estimate the occurrence of lung cancer in Hungary based on a retrospective review of the National Health Insurance Fund (NHIF) database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between 1 Jan 2011 and 31 Dec 2016. Age-standardized incidence and mortality rates were calculated using both the 1976 and 2013 European Standard Populations (ESP). Results: Between 2011 and 2016, 6,996 - 7,158 new lung cancer cases were recorded in the NHIF database annually, and 6,045 - 6,465 all-cause deaths occurred per year. Age-adjusted incidence rates were 115.7-101.6/100,000 person-years among men (ESP 1976: 84.7-72.6), showing a mean annual change of - 2.26% (p = 0.008). Incidence rates among women increased from 48.3 to 50.3/100,000 person-years (ESP 1976: 36.9-38.0), corresponding to a mean annual change of 1.23% (p = 0.028). Age-standardized mortality rates varied between 103.8 and 97.2/100,000 person-years (ESP 1976: 72.8-69.7) in men and between 38.3 and 42.7/100,000 person-years (ESP 1976: 27.8-29.3) in women. Conclusion: Age-standardized incidence and mortality rates of lung cancer in Hungary were found to be high compared to Western-European countries, but lower than those reported by previous publications. The incidence of lung cancer decreased in men, while there was an increase in incidence and mortality among female lung cancer patients.

Apparent efficiency of serially coupled columns in isocratic and gradient elution modes.

The goal of this work was to understand the variation of apparent efficiency when serially coupling columns with identical stationary phase chemistries, but with differences in their kinetic performance. For this purpose, a mathematical treatment was developed both for isocratic and gradient modes to assess the change in plate numbers and peak widths when coupling arbitrary several columns. To validate the theory, experiments were also carried out using various mixtures of compounds, on columns packed with different particle sizes, to mimic highly efficient (new, not used) and poorly efficient columns (used one with many injections). Excellent agreement was found between measured and calculated peak widths. The average error in prediction was about 5% (which may be explained by the additional volume of the coupling tubes). In isocratic mode, the plate numbers are not additive when the coupled columns possess different efficiencies, and a limiting plate count value can be calculated depending on the efficiency and length of the individual columns. Theoretical efficiency limit can also be determined assuming one column in the row with infinite efficiency. In gradient elution mode, the columns' order has a role (non-symmetrical system). When the last column has high enough efficiency, the gradient band compression effect may outperform the competing band broadening caused by dispersive and diffusive processes (peak sharpening). Therefore, in gradient mode, the columns should generally be sequentially placed according to their increasing efficiency.

Influence of pressure and temperature on molar volume and retention properties of peptides in ultra-high pressure liquid chromatography.

In this study, pressure induced changes in retention were measured for model peptides possessing molecular weights between ∼1 and ∼4kDa. The goal of the present work was to evaluate if such changes were only attributed to the variation of molar volume and if they could be estimated prior to the experiments, using theoretical models. Restrictor tubing was employed to generate pressures up to 1000bar and experiments were conducted for mobile phase temperatures comprised between 30 and 80°C. As expected, the retention increases significantly with pressure, up to 200% for glucagon at around 1000bar compared to ∼100bar. The obtained data were fitted with a theoretical model and the determination coefficients were excellent (r(2)>0.9992) for the peptides at various temperatures. On the other hand, the pressure induced change in retention was found to be temperature dependent and was more pronounced at 30°C vs. 60 or 80°C. Finally, using the proposed model, it was possible to easily estimate the pressure induced increase in retention for any peptide and mobile phase temperature. This allows to easily estimating the expected change in retention, when increasing the column length under UHPLC conditions.

On the optimization of the shell thickness of superficially porous particles.

The thickness of the porous shells of superficially porous particles influences the separation power of columns packed with these packing materials. Models of the mass transfer kinetics across porous adsorbents permit the prediction of the HETP curves of columns packed with particles having shells of different thicknesses, for molecules of different sizes. Decreasing the thickness of the porous layer potentially results in lower values of the "C-term" of the HETP curve and of the minimum of these curves. The Poppe plots calculated under isocratic and gradient conditions show that the separation power of columns packed with superficially porous particles increases significantly with decreasing thickness of the porous layer but this increase is more important for larger than for smaller molecules. The resolution between pairs of compounds increases at constant values of their retention factors when the strength of the eluent must be reduced to compensate for the decrease of their retention that is caused by the reduction of the surface area of the stationary phase. Thus, the separation power of columns packed with superficially porous particles increases with decreasing shell thickness. In contrast, if analysts do not compensate for the retention decrease, the resolution between small molecular weight compounds becomes worse with thin than with thick superficially porous particles. Finally, the importance of using instruments providing low extra-column band broadening contributions is stressed.

Determination of carbon monoxide concentration and total pressure in gas cavities in the silica glass body of light bulbs by FT-IR spectrometry.

Fourier transform infrared (FT-IR) spectroscopy has been adapted to control the quality of light bulbs made from silica glass. Such light bulbs contain a molybdenum accessory which, if contaminated with carbon, during the melting procedure of bulb fabrication, can cause the production of carbon monoxide. This CO can be trapped in small gas cavities in the silica glass body of the bulb. A method has been developed for the detection of CO and the total pressure within these gas cavities by traditional FT-IR spectrometry using a spectral resolution of 0.5 cm(-1). The concentration of CO was determined by using a classical least-squares (CLS) method, and the accuracy of concentration determination is reported for the case with sample and reference spectra recorded at different pressures. The total pressure in the cavities was established by two different methods: either by CLS fitting of reference spectra to sample spectra or fitting a Voigt line shape function to the spectral lines within the CO fundamental stretching band. In the latter method, the width of the lines was determined and pressure-broadening coefficients are given and compared with high-resolution data from the literature. According to the measurements, 0.55-0.80 atm total pressure and 0.8-4.0% (v/v) CO was determined in the gas cavities. This method can also be applied to determine the total pressure in similar enclosed spaces in which an appropriate indicator gas component exists.