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Abstract
SZJ-1207 is an antidepressant natural product with a steroidal structure extracted from Stephanotis mucronata. It is a novel antidepressant candidate molecule and all its pharmacokinetic properties have not been reported. In this pharmacokinetic study in mice following oral administration, an accurate and sensitive UPLC-MS/MS method was established and evaluated to measure SZJ-1207 concentrations in mouse plasma and brain samples. The results provide information regarding the pharmacokinetics of SZJ-1207 as a potential antidepressant.
Az „Alsóban az élet” című hazai talajállapotot célzó közösségi tudomány program első tapasztalatai és eredményei
The First experiences and results of the Hungarian citizen science program (’Life in Undies’) aimed at soil properties
A közösségi tudomány – citizen science – már évtizedek óta működő kutatási forma, ahol egy-egy kutatás a lakosság segítségével valósul meg. Az „Alsóban az élet” kampány az érdeklődők bevonásával 2021 tavaszán indult hazánkban. A kutatásban résztvevők kézhez kaptak egy pamut alsóneműt, amelyet kb. 20 cm-es mélységben kellett elásniuk, ezzel „táplálékot” szolgáltatva a talajlakó élőlények számára. Több mint két hónap elteltével az alsónemű kiásása után megfigyelhetők a bomlási jelek, amelyek mint indikátor jelzik a talajélet aktivitását, közvetett módon a talaj egészségi állapotát. A visszamaradt alsóneműk digitális fotójának elemzésével becsülhető a talajlakó élőlények munkája az alsónadrágok bomlásának százalékos aránya alapján.
A közösségi médiában megjelent felhívások és célzott csoporthirdetések segítségével mintegy 1193-an jelentkeztek a programra összesen 1966 helyszínnel, ezzel országos lefedettséget biztosítva a kutatás részére. Az adatok elemzése alapján a gondozott konyhakertekben elásott pamut alsók mutatták a legnagyobb átlagos bomlási értékeket (27,67%). Talajtípust tekintve a réti talajok és a közép- és délkeleteurópai barna erdő-, valamint a csernozjom-, és a váztalajok (köztük nagyrészt a humuszos homoktalajok) esetén tapasztaltuk a legmagasabb, közel azonos, 25,47%; 25,43%; 24,22%; 24,21%-os bomlási értéket. A programban résztvevő helyszínek közül a legnagyobb mértékű bomlás (93%) konyhakert hasznosítású (mulcsozott veteményes és polikultúra ágyás) váztalajon (homoktalajon) volt megfigyelhető. Az országos átlagos bomlási érték 24,57% volt. A bomlási adatok alapján eredménytérképet szerkesztettünk Magyarország teljes területére, melyet nyilvánossá tettünk, s a résztvevőknek a visszaküldött fotó feldolgozása alapján rövid, a saját talajának biológiai aktivitását minősítő válaszlevelet küldtünk.
Abstract
The retention behaviour of scopolamine (hyoscine) and its related compounds (norhyoscine, atropine, homatropine, and noratropine) was investigated on the silica-based HPLC stationary phase. The retention of investigated tropane alkaloids was interpreted by using the Soczewiński-Wachtmeister equation. A high correlation between the retention parameter (log k) and lipophilicity (log P) (R = 0.9923) confirms the significant influence of hydrophobic interactions on the retention behaviour of the aforementioned compounds. It was found that by increasing the acetonitrile fraction, a decrease in retention of the more polar epoxide derivatives (scopolamine, norhyoscine) and an increase in retention of the more lipophilic derivatives (atropine, noratropine, homatropine) is obtained. The best separation of the tropane alkaloids was achieved by a simple procedure that involved a mobile phase composed of acetonitrile and 40 mM ammonium acetate/0.05% TEA, pH 6.5; 50:50 v/v. Selected conditions were assumed for the determination of scopolamine hydrochloride in the eye drops (Scopolamini hydrobromidum 0.25%). The method was validated and it was found as selective, sensitive, precise, accurate, and robust for the further qualitative analysis of the scopolamine-related compounds.
Abstract
In this study, we report the systematic approach for characterization of two major degradant impurities, which are not listed in any compendia and were formed during the stability studies of Dihydroergotamine mesylate injection (DHE). An ion-pair UPLC chromatographic method was developed to quantify the related substances present in the DHE injection drug product. The same was used to monitor the impurity profiling during its stability. The two unknown impurities were observed at RRT about 0.08 (Impurity-1) and RRT about 0.80 (Impurity-5) and found to be significantly increasing on stability. Forced degradation studies revealed the nature of the impurity and conditions required for enriching them. A Mass compatible HPLC method was developed to quantify only these two impurities using 25% ammonia and formic acid in water. Their mass numbers were identified using LC MS/MS with triple quadruple mass spectrometer coupled with a HPLC. These two impurities were then isolated from enriched products using preparative HPLC. These impurities were then characterized using Mass and NMR analysis along with Q-TOF elemental analysis.
Abstract
Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and represent important antibacterial drug targets. To be successful as drug candidates, newly synthesized compounds must possess optimal lipophilicity, which enables efficient delivery to the site of action. In this study, retention behavior of twenty-three previously synthesized dual DNA gyrase and topoisomerase IV inhibitors was tested in RP-HPLC system, consisting of C8 column and acetonitrile/phosphate buffer (pH 5.5 and pH 7.4) mobile phase. logD was calculated at both pH values and the best correlation with logD was obtained for retention parameter φ0, indicating that this RP-HPLC system could be used as an alternative to the shake-flask determination of lipophilicity. Subsequent QSRR analysis revealed that intrinsic lipophilicity (logP) and molecular weight (bcutm13) have a positive, while solubility (bcutp3) has a negative influence on this retention parameter.
Hígtrágya komplex baktérium-kezelésének hatása egyes beltartalmi és ökotoxikológiai tulajdonságokra
The effect of complex bacterial treatment of slurry on content and ecotoxicological properties
Kutatásunk témája az NCH Magyarország Kft. által forgalmazott baktériumos hígtrágyakezelési rendszer összehasonlító ökotoxikológiai vizsgálata. A kísérletet egy szarvasmarha borjúnevelő telepen végeztük 0–6 hónapos korcsoportú szekcióban. A tabletta formában rendelkezésünkre álló baktérium törzseket egy tartályban felszaporítottuk és hetente adagoltuk az aknában összegyűlő hígtrágyához. A kezelés célja volt, hogy a baktériumok elősegítsék a trágya homogenizációját, a szagcsökkentést és a szerves szennyeződések lebontását. Az ökotoxikológiai vizsgálatokat a trágyakezelés előtt, alatt és után, három mintavételi időben végeztük el.
A kutatásunk eredményeként elmondhatjuk, hogy a hígtrágyakezelés során a beltartalmi értékek jelentősen növekedtek, főként a nitrogénformák, a biológiai oxigénigény és a szárazanyagtartalom. Az ösztrogén hatás megléte számottevő maradt a kezelés végére is. A fitotoxicitási vizsgálat alapján mindegyik növény, szár- és gyökérnövekedésére pozitív hatással volt a trágyakezelés. A talajtoxicitási teszt eredménye bizonyította, hogy magasabb hígítás mellett veszti el a kezeletlen hígtrágya az érzékeny baktériumok élettevékenységére is kiterjedő gátló hatását. A békalencse vizsgálat során összességében elmondható, hogy 150× hígítás fölött megszűnik a hígtrágya gátló hatása mindhárom alkalommal vett minta esetében. Az alga növekedésgátlására a hígtrágya stagnáló-gátló tendenciát mutatott a kezelés alatt.
Eredményeink alapján arra a következtetésre jutottunk, hogy a vizsgált hígtrágyakezelési módszer a homogenitás, szagtalanítás és a szerves anyagok bontása során eredményes volt. Azonban javasolt magasabb hígítási arányban vagy magas talajvíztartalom mellett kijuttatni a földekre. A hormonhatású anyagok eltávolítására vonatkozólag további vizsgálatok szükségesek, melyek alapján majd javaslatokat lehet kidolgozni a gazdák számára.
Abstract
Rationale
The bark of Eucommia ulmoides and the roots of Achyranthes bidentata are commonly used in traditional Chinese medicine, and their pairing appears in many traditional Chinese medicine formulas as a recognized compatible unit. However, the changes and interactions of the main components of these two formulas when paired remain unclear, and there is currently no standard or method for their quality control and assessment of pharmacological effects.
Methods
An optimized ultra-high-performance liquid chromatography triple-quadrupole mass spectrometry (UHPLC-MS/MS) method was established for the simultaneous identification of 10 components in E. ulmoides and A. bidentata using in vitro and in vivo models. Tributyltin methacrylate was the internal standard solution, and the blood samples were treated by an organic solvent precipitation method. Gradient elution was conducted on a C18 column at 25 °C with 0.1% formic acid water:acetonitrile as the mobile phase at a flow rate of 0.5 mL min−1. Dynamic multiple response monitoring was performed in negative-ion mode using an Agilent Jet Stream electrospray ionization ion source.
Results
In negative-ion detection mode, eucommiol exhibited a good response, and the isomers ginsenoside Ro and achyranthoside C could also be well separated. The developed method accurately detected the five components with a low blood content. Compared to controls, the levels of ginsenoside Ro, chikusetsusaponin Ⅳa, and achyranthoside C increased; the contents of geniposidic acid and pinoresinol diglucoside were unchanged; and the levels of eucommiol, geniposide, β-ecdysterone, genipin, and achyranthoside D decreased in vitro. In vivo, the contents of geniposidic acid, geniposide, pinoresinol diglucoside, and β-ecdysterone were reduced; the contents of eucommiol and ginsenoside Ro were unchanged; and those of achyranthoside D, chikusetsusaponin Ⅳa, and achyranthoside C increased compared to the corresponding levels in the internal control.
Conclusions
A method for the quality control of the E. ulmoides-A. bidentata drug pair was established for the first time and the main components in 10 drug pairs could be determined simultaneously in vitro and in vivo. These findings show that the E. ulmoides and A. bidentata drug pair cause a compositional change, providing new ideas for the development of this combination to improve clinical efficacy.
Abstract
We developed and validated a sensitive, heart-cutting, two-dimensional liquid chromatography–tandem mass spectrometry (2D-LC‒MS/MS) method to determine the concentration of mometasone furoate in human plasma after nasal spray administration. Isotopically labeled mometasone furoate-13C,d6 was used as an internal standard (IS). Plasma samples were prepared using a solid-phase extraction (SPE) method. With this 2D-LC strategy, the analytes were trapped in the first dimension (1D) column, and only judiciously selected portions of the 1D effluent were transferred to the second dimension (2D) column for further separation to obtain high-resolution information. MS/MS quantification was performed in positive ionization mode via multiple-reaction monitoring (MRM). This analytical method was fully validated according to related regulatory guidance, and the results showed that the method is robust and sensitive enough for pharmacokinetic investigation of mometasone furoate with satisfactory linearity from 0.25 to 30 pg mL−1. This method was successfully applied to a bioequivalence (BE) study of mometasone furoate aqueous nasal sprays in healthy volunteers.
Abstract
A simple, rapid, sensitive and eco-friendly liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of free cordycepin (3′-deoxyadenosine) and isocordycepin (2′-deoxyadenosine) in 10 kinds of Cordyceps samples. The samples were prepared by ultrasonic extraction at 75 °C for 30 min with boiling water as the extraction solvent. The LC separation was performed on an Agilent poroshell 120 SB-Aq C18 column (3.0 × 50 mm, 2.7 μm) in isocratic mode with an eco-friendly mobile phase (2% ethanol containing 0.2% acetic acid) at a flow rate of 0.6 mL min−1, and detected by MS/MS in positive mode with multiple reaction monitoring (MRM). The developed method showed good linearity (r > 0.9990), sensitivity (LODs = 0.04 pg, LOQ = 0.1 pg), precision (RSD ≤ 3.8%) and stability (RSD ≤ 3.6%). The recoveries of developed method were 94.4–109.5% (RSD ≤ 5.5%). Compared with reported methods, the current method was rapid (less than 35% analytical time), sensitive (more than 5 folds), and eco-friendly (less than 10 μL harmful organic solvent). 10 different kinds of Cordyceps samples (40 batches) were tested by the developed method. Codycepin was only found in Cordyceps millitaris and C. millitaris fruiting body, and isocordycepin was detected in Cordyceps sinensis and other 6 Cordyceps samples. The developed method would be an improved method for the quality evaluation of Cordyceps samples.
Abstract
The study was aimed to validate and optimize high performance liquid chromatographic (HPLC) method for the determination of coumarin-3-carboxylic acid (C3A) in the heart and liver issue of Sprague-Dawley (SD) rats after intragastric administration of extractive of leaves of Ficus virens var sublanceolata. And simple ADME and target prediction analyses were performed for C3A. Ethyl acetate was employed to precipitate protein with appropriate sensitivity and acceptable matrix effects. The satisfactory separation was developed on an ODS2 column (4.6 mm × 250 mm, 5 μm) by gradient elution with a methanol-acetic acid solution (pH = 3.0) as the mobile phase. The flow rate was 1.0 mL min−1, the column temperature was maintained at 30 ± 2 °C, the injection volume was 20 μL, and the detection wavelength was set as 309 nm. The method was fully validated in terms of selectivity, linearity, accuracy, precision, extraction recovery and stability. The results of the ADME analysis found that C3A has excellent characteristics of drug-likeness, consistent with good bio-absorption. And the predicted 12 target protein belongs to the amine oxidoreductase and carbonic anhydrase target class. This method is simple, rapid, sensitive, and accurate for the determination of coumarin-3-carboxylic acid in the heart and liver tissue of SD rats.
