Determination of free and total warfarin concentrations in plasma using UPLC MS/MS and its application to a patient samples

Warfarin is routinely monitored by assessing its pharmacologic effects on the international normalized ratio. However, having a patient with INR not responding to increasing warfarin dose mandates a direct measurement of warfarin concentrations (total and free) for better patient clinical management of warfarin therapy. Therefore, a new fully validated specific, precise and accurate ultra-performance liquid chromatography tandem mass spectrometry was developed for the determination of free and total warfarin in human plasma. Free warfarin was measured in plasma filtrate, prepared by ultrafiltration, and sample pretreatment involved protein precipitation with acetonitrile. Linear response (r(2) ≥0.99) was observed over the studied range of free and total warfarin, with the lower limit of detection of 0.25 ng/mL. The intra- and inter-day precision (relative standard deviation) values were <10% and the accuracy (relative error) was ≤6.6 for free and total warfarin. There was no significant difference (p>0.05) between inter- and intra-day studies for the free and total warfarin, which confirmed the reproducibility of the assay method. The mean extraction efficiency was 88.6-107.2% of free and total warfarin. The assay was sensitive to follow warfarin pharmacokinetics (free and total) in a patient with resistance to warfarin up to 24 h after a daily dose of warfarin.     

Parametric approach to optimal control

We consider the optimal control problem from view point of parametric aspects. We have examined two cases of the parameterized problems. First case describes the situation when the objective functional contains time t as a parameter. We also show how to apply the parametric optimization techniques, such as pathfollowing methods, for finding a nominal optimal control path.     

Mechanistic Insights into the Ameliorative Effect of Cichoriin on Diabetic Rats—Assisted with an In Silico Approach

Type 2 diabetes mellitus is considered to be a substantial socioeconomic burden worldwide on both patients and governments. Coumarins are biomolecules with a diversity of biological activities. The current investigation aimed to explore the ameliorative effects of cichoriin, which is a type of coumarin, on high-fat diet/streptozotocin (HFD/STZ)-induced diabetic rats. Methods: Rats were allocated into five groups. Group I was considered as the control group, while the other groups were HFD/STZ-induced diabetic rats. Group II was assigned as the diabetic control. Groups III and IV were treated with cichoriin (50 or 100 mg/kg, respectively). Group V received glibenclamide (5 mg/kg) (as a positive control). The blood glucose (BG), serum insulin, triglycerides (TG), total cholesterol (TC), total antioxidant capacity (TAC), catalase, hepatic superoxide dismutase (SOD) and content of malondialdehyde (MDA) were assessed. Histopathological and immunohistochemistry analysis of pancreatic tissue were performed. mRNA and protein expressions of GLUT4, AMPK, and PI3K were estimated. Results: Cichoriin treatment ameliorated HFD/STZ-induced diabetic conditions and mitigated the histopathological characteristics of the pancreas, as well as increasing pancreatic insulin expression. This decreased the levels of BG, TG, TC, and MDA and improved the TAC, catalase and SOD contents. Cichoriin demonstrated upregulation of mRNA and protein expressions of GLUT4, AMPK, and PI3K. The in silico binding of cichoriin with GLUT4, AMPK, and PI3K supported the possible current activities. Conclusion: Collectively, this work highlighted the potential role of cichoriin in mitigating HFD/STZ-induced diabetic conditions and showed it to be a valuable product.     

Flavonoids of Alcea rosea L. and their immune stimulant,antioxidant and cytotoxic activities on hepatocellular carcinoma HepG-2 cell line

Alcea rosea L. is widely cultivated in gardens of Egypt as an ornamental plant and it has a great history of folkloric medicinal uses. In the present work, phytochemical investigation of the alcoholic extract of the flowers of A. rosea L. led to the isolation of six flavonoids (1–6). Dihydrokaempferol-4′-O-β-d-glucopyranoside (1), dihydrokaempferol (2), kaempferol-3-O-[6″-(E-coumaroyl)]-β-d-glucopyranoside (3), kaempferol-3-O-β-d-glucopyranoside (4), Apigenin (5) and kaempferol-3-O-α-l-rhamnopyranosyl-(1′″→6″)-β-d-glucopyranoside (6). Four of the isolated compounds were evaluated for their antioxidant, immunostimulant and cytotoxic activities against HepG-2 cell line. Compound (3) showed potent cytotoxic activity against HepG-2 cell line with high selectivity towards hepatocellular carcinoma in vitro (with IC₅₀ = 3.8 μg/mL). Compounds 1 and 2 exhibited significant antioxidant activity and compound 4 showed a significant immune stimulant activity. Compound 1 is isolated for the first time from genus Alcea and this is the first report for its biological investigation.     

Steroid sapogenins. XII

Summary An effective procedure is described for the resolution of steroid sapogenins as acetates on silver nitrate-impregnated alumina and silica gel plates. The resolutions are achieved by means of suitable solvent systems which are used either singly or in combination. A p-anisaldehyde reagent is employed for spraying. Clearly defined and well separated spots are obtained independent of the hydroxyl content. The method is rapid and appears adaptable to screening purposes.

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Zusammenfassung Zur Identifizierung von Steroidsapogeninen wird die Dünnschichtchromatographie der Acetate auf Silicagel- oder Aluminiumoxidschichten empfohlen, die mit Silbernitrat imprägniert sind. Zur Entwicklung wird eine Reihe von Lösungsmittelgemischen angegeben, die allein oder in Kombination angewendet werden. Der Nachweis erfolgt mit einem p-Anisaldehyd-Reagens. Unabhängig vom Hydroxylgehalt erhält man scharf begrenzte und gut getrennte Flecke. Die Methode erlaubt eine rasche Orientierung über die Zusammensetzung eines Gemisches.

     

The search for internal isotopic tracers in metallurgical materials

In a search for internal isotopic tracers in metallurgical materials a group of elements has been chosen which can be determined by the neutron activation method with the higher sensitivity. A method has been developed for the determination of W, As, Au, La, In, Sc, Re and Ir in metallurgical materials. The separation of the elements was carried out using extraction and precipitation. The determination of the elements was carried out in samples of chamotte brick and washed ores. The limits of the determination of the elements are of the order of 10⁻¹¹ g for Au, 10⁻¹⁰ g for In and La and 10⁻⁹ g for As, W, Sc, Re and Ir. The large scatter of the results indicates the inhomogeneity of the materials analyzed.     

Thermal decomposition of ammonium permanganate

The parent material, ammonium permanganate, was carefully decomposed in air at 120°. The product, referred to as the starting material (SM), was then subjected to thermal treatment in air for 5 hr in the temperature range 150–1200°. Chemical analysis of SM indicated that the main decomposition product of NH₄MnO₄ was Mn₂O₃, together with MnO₂, NH₄NO₃, H₂O and O₂. Mn₃O₄ started to form at 900°. The infrared spectra of various calcination products revealed the retention of NH ₄ ⁺ in the lattice structure up to 300°, and reflected the presence of excess oxygen as coordinated O ₂ ^– . The TG, DTA and IRA results on SM supported the chemical analysis data. X-ray analysis was carried out for phase identification and to follow transformations and the formation of a solid solution between MnO₂ and Mn₂O₃.

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Zusammenfassung Die Muttersubstanz, Aramoniumpermanganat, wurde in Luft bei 120° vorsichtig zersetzt. Das dabei erhaltene Ausgangsmaterial (SM) wurde danach in Luft 5 Stunden im Temperaturbereich von 150–1200° thermisch behandelt. Die chemische Analyse von SM ergab, daß als Hauptprodukt der Zersetzung von NH₄MnO₄, Mn₂O₃ auftritt neben MnO₂, NH₄NO₃, H₂O und O₂. Die Bildung von Mn₃O₄ beginnt bei 900°. Aus Infrarotspektren verschiedener Kalzinierungsprodukte ist ersichtlich, daß in der Gitterstruktur NH ₄ ⁺ bis 300° zurückgehalten wird und überschüssiger Sauerstoff in Form von koordiniertem O₂ vorliegt. Die Ergebnisse der TG-, DTA- und IRA-Untersuchungen von SM bestätigen Daten der chemischen Analyse. Mittels Röntgenanalyse wurden die Phasen identifiziert und der Verlauf der Phasenübergänge und der Bildung einer festen Lösung zwischen MnO₂ und Mn₂O₃ verfolgt.

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120°. , , 5 150–1200°. , , , , . 900° Mn₃O₄. 300° - O ₂ ^– . , . , .

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Paper presented at the World Conference on Thermal Analysis, Madeira (Portugal), 1986.     

Dapson in Heterocyclic Chemistry,Part I: Novel Synthesis of Sulfone Biscompounds for Antimicrobial and Antitumor Activities

This article describes the synthesis of some novel sulfone bis-compounds bearing the biologically active thioether 3–6 ; thioureido 7, 8, 15, 16; triazole 10, 11; thiosemicarbazido 9, 12, 13; and 1,3,4-thiadiazole 14, 17 moieties starting with 4,4′-diisothiocyanato-1,1-diphenylsulfone 2. The structures of newly synthesized compounds were confirmed by elemental analysis, IR, ¹ H-NMR and mass spectral data. Compound 3 was found to be the most active compound against Escherichia coli. Also, compound 15 acted as potent cytotoxic agent.     

Theoretical Model for Surface Forces between Cytosine and CNT(6,6-6) Nanotube: Geometry Optimization,Molecular Structure,Intermolecular Hydrogen Bond,Spectroscopic (NMR,UV/Vis,Excited State), FMO,MEP, and HOMO–LUMO Investigations

Russian Journal of Physical Chemistry A - In the present work, the adsorption of the molecule cytosine on carbon nanotube [CNT] (6,6-6) was investigated for the first time using density functional...