Analytical procedures to be used in pharmaceutical quality control have to be validated strictly in accordance with highly formalized standards and guidance. Manuscripts submitted for publication presenting new procedures must therefore describe the corresponding validation characteristics and the validation approach and procedure accordingly. Interestingly, many of these manuscripts and — what is worse — already published (and therefore accepted) articles in various periodicals are characterized by several typical methodological failures and misconceptions — even though authors have regularly been informed of such mistakes in the hope they can be avoided. The corresponding ICH guideline seems to be well-known, and is frequently cited in these manuscripts, but to some extent is not fully understood and is even partially neglected. In this paper the authors present a collection of typical failures, misconceptions, and misleading data captured as reviewers and readers of published articles over the last two years, thus giving a survey of the most frequent problems of TLC/HPTLC validation. Moreover, the authors provide a list of references describing optimum approaches to validation of specific TLC/HPTLC procedures. We suggest these are followed in addition to the general concepts of the ICH guideline.
The acidic visualization methods most often used for steroids have been optimized and compared. Sulfuric acid at three different concentrations, phosphomolybdic acid, and phosphoric acid, with different heating temperatures for different times, have been examined as reagents for visualization of seven steroids separated by OPLC on HPTLC silica gel as adsorbent. For sulfuric and phosphoric acids the chromatograms were evaluated by inspection under long-wavelength UV light (366 nm). For phosphomolybdic acid the chromatograms were evaluated in daylight. It was found that visualization at higher temperatures for shorter periods usually results in greater sensitivity, although heating for longer periods at lower temperatures results in a more stable, robust visualization.
The Varieties of Capitalism (VoC) literature has recently manifested a dynamic development. Among others, the member states of the European Union (EU) have been studied extensively from this viewpoint, and main capitalism models have been identified. Yet, the global financial and economic crisis and its aftermath in Europe have impacted the member states' economies, typically in asymmetric ways and, in 2020, a highly diverse EU faced the COVID-19 induced economic crisis.
Our study investigates the EU member states from a perspective different from the existing research on VoC in Europe: our starting point is the macroeconomic decomposition of GDP. Our findings draw up a categorisation somewhat different from the previous results: while the core of the EU is rather consistent and homogenous, clusters of the periphery do not fully coincide with geography and earlier typisations; there are also single outliers and ‘New tigers of Europe’ emerging. Nevertheless, the core-periphery divide still stands overall.
An OPLC purity test suitable for routine analysis of norethisterone bulk drug substance and in tablets has been developed. Separation was performed on a fine-particle silica gel adsorbent layer by continuous development with
-hexane and butyl acetate-chloroform, 85 + 15 (
), as mobile phases. Visualization of the chromatogram by use of sulfuric acid enables detection of less than 0.05% of possible impurities by use of long-wave UV illumination. The selectivity and efficiency of this OPLC method were compared with those of the pharmacopeial TLC methods and those of HPLC method.
The effect of cold-stress (2°C, 7 days cold-hardening) on the level of polyamines in different varieties of wheat and genetically modified wheat samples (chromosome substitution lines, deletion lines, recombinant lines) has been investigated. Biogenic amines (spermine, spermidine, putrescine, and agmatine) were determined as the dansyl derivatives by stepwise gradient elution with the Personal OPLC BS 50 Chromatograph. Short-term cold-hardening caused characteristic changes in free polyamine content of wheat genotypes. The total free polyamine content was significantly lower in the cold-hardened samples than in the control samples. It seems that accumulation of spermine and agmatine might be good markers of cold sensitivity.
A vérplazma emelkedett lipidszintje a cardiovascularis betegségek kialakulásának egyik legfőbb kockázati tényezője, amelyet elsődleges halálokként tartanak számon. Az apolipoprotein E a lipidek szállításában vesz részt a vérben, ezért polimorfizmusai befolyásolják a plazma lipidösszetételét. Az apolipoprotein E génjének három leggyakoribb alléljai az e2, az e3 és az e4. A két nem vad típusú allél, az e2 és e4 közül az utóbbi számos vizsgálat eredménye szerint szerepet játszik a szív-ér rendszeri betegségek, valamint az Alzheimer-kór kialakulásában. Az e2/e2 homozigóta genotípust a 3-as típusú hyperlipoproteinaemia egyik előidézőjeként említik egyes tanulmányok. Mivel az apolipoprotein E nemcsak a lipidanyagcsere útján, hanem más biokémiai útvonalakon is befolyásolhatja a cardiovascularis betegségek manifesztációját, így kiemelkedő fontosságú lehet ezen anyagcsereutak molekuláris hátterének felderítése. Orv. Hetil., 2012, 153, 2070–2076.
Two wheat cultivars (
L. cv. Chinese Spring and Cappelle Desprez) differing in drought stress tolerance were treated with two concentrations of cadmium (10
to investigate whether there is also any difference in their heavy-metal tolerance. Overpressured layer chromatography (OPLC) with off-line fluorescence detection was used to monitor cadmium stress-induced changes in the polyamine content of wheat seedlings. Significant differences were found between the spermidine (Spd) and putrescine (Put) content of the two wheat cultivars. The Spd content of the moderately drought-tolerant Chinese Spring increased both in shoots and roots at the higher Cd concentration compared with the control whereas in the drought-sensitive Cappelle Desprez the Spd level was reduced by both Cd treatments. Put content increased with the amount of Cd to which the roots of Chinese Spring wheat were exposed. In the Cappelle Desprez cultivar the Put content of both organs was higher at both Cd concentrations compared with the control.
A semiquantitative OPLC purity test has been developed for inprocess control of nandrolone and compared with other chromatographic methods. TLC was not sufficiently selective, a key impurity with low UV absorption could not be detected by HPLC, and nandrolone was slightly degraded during gas chromatography. OPLC proved to be a suitable means of testing for all potential impurities in nandrolone. The separation was performed by multiple development on fine-particle silica gel with cyclohexane-ethyl acetate-chloroform, 50 + 25 + 25 (
), as mobile phase. After spraying the chromatograms with sulfuric acid, then heating, the impurities could be sensitively detected by visual inspection in long-wave UV light. Detection limits were ≤0.01 μg.
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide pandemic, due to its great capacity to invade the human body. Previous studies have shown that the primary route of invasion of this virus is the human respiratory tract via the co-expression of ACE2 receptor and TMPRSS2, a serine protease on the cellular surface. Interestingly, this condition is present not only on the respiratory epithelium but on the conjunctival mucosa, as well. Thus, we hypothesized that SARS-CoV-2 is present on the conjunctival mucosa.
To prove that SARS-CoV-2 can be detected in the conjunctiva.
Previously nasopharyngeal swab-sample based real-time polymerase chain reaction (PCR) positive COVID-19 infected patients were selected at the COVID Care Centers of Semmelweis University, Budapest, Hungary. The study was approved by the ethical committee of Semmelweis University. During their recovery, both nasopharyngeal and conjunctival swab-samples were taken and PCR method was used to detect the presence of SARS-CoV-2 RNA. Appropriate statistical analysis was performed.
The study population consisted of 97 patients, 49 females (50.5%) and 48 males (49.5%), with a mean age of 67.2 ± 11.9 years. During recovery, with nasopharyngeal swabs, the PCR test was positive in 55 cases (56.70%), whereas with conjunctival swabs it was positive in 8 cases (8.25%). Both tests were positive in 5 cases (5.15%). In some patients, ocular symptoms were observed as well. The rest of the patients (29 cases) had negative nasopharyngeal PCR tests during recovery.
Although only in few cases, the data of the present study provides a proof of concept that SARS-CoV-2 can be present on the conjunctival mucosa even in nasopharyngeal negative patients, a finding, which can have clinical importance. Also, on the basis of these findings one can hypothesize that - in addition to the respiratory tract – the conjunctiva can be an entrance route for SARS-CoV-2 to the human body. Thus, in high-risk conditions, in addition to covering the mouth and nose with mask, the protection of the eyes is also strongly recommended.
A szív-ér rendszeri megbetegedések világszerte a leggyakoribb halálozási okok közé tartoznak. Az utóbbi évek tudományos eredményei arra utalnak, hogy a hyperhomocystinaemia a szív-ér rendszeri betegségek egyik jelentős kockázati tényezője. A homocisztein és a folsav metabolizmusát befolyásoló gének közül a metilén-tetrahidrofolát-reduktáz (MTHFR) polimorfizmusai – az MTHFR C677T és az MTHFR A1298C – összefüggésbe hozhatóak a cardiovascularis betegségekkel. A magas vérnyomás kialakulásában az MTHFR C677T polimorfizmusa is hajlamosító tényező lehet. Nem egyértelmű ugyanakkor az összefüggés a hyperhomocystinaemia és az MTHFR említett génvariánsai között. A legújabb kutatási eredmények szerint az 5-metil-tetrahidrofolát (5-MTHF) is befolyásolja az endothelfunkciókat. Így valószínűsíthető, hogy az MTHFR polimorfizmusai a homociszteintől függetlenül is hajlamosítanak a magas vérnyomásra és a szív-ér rendszeri megbetegedések kialakulására. Ennek tükrében kiemelkedő fontosságú lehet a folsavanyagcserében részt vevő génpolimorfizmusok és a cardiovascularis kockázati tényezők közötti kapcsolat vizsgálata és a molekuláris patomechanizmusok feltárása. Orv. Hetil., 2012, 153, 445–453.