Novel and sensitive UPLC–MS/MS method for quantification of sofosbuvir in human plasma: application to a bioequivalence study

A novel and sensitive LC–MS/MS method was developed and validated for determination of sofosbuvir (SF) using eplerenone as an internal standard. The Xevo TQD LC–MS/MS was operated under the multiple‐reaction monitoring mode using electrospray ionization. Extraction with tert‐butyl methyl ether was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC BEH C₁₈ (50 × 2.1 mm, 1.7 μm) column by pumping 0.1% formic acid and acetonitrile in an isocratic mode at a flow rate of 0.35 mL/min. Method validation was performed as per the US Food and Drug Administration guidelines and the standard curves were found to be linear in the range of 0.25–3500 ng/mL for SF. The intra‐ and inter‐day precision and accuracy results were within the acceptable limits. A very short run time of 1 min made it possible to analyze more than 500 human plasma samples per day. A very low quantification limit of SF allowed the applicability of the developed method for determination of SF in a bioequivalence study in human volunteers. Copyright © 2016 John Wiley & Sons, Ltd.     

Determination of Sumatriptan and Zolmitriptan in Presence of Their Corresponding Degradation Products by HPTLC Methods

Accurate, sensitive, and precise high performance thin layer chromatographic (HPTLC) methods were developed and validated for the determination of sumatriptan and zolmitriptan in presence of their degradation products. Sumatriptan was separated from its degradation products and analyzed on TLC silica gel 60 F₂₅₄ plates using chloroform–ethyl acetate–methanol–ammonia (4:3:3:0.1, v/v) as a developing system followed by densitometric measurement of the bands at 228 nm. Zolmitriptan was determined using chloroform–ethyl acetate–methanol–ammonia (3:3:3:1, v/v) as a developing system followed by densitometric measurement at 222 nm. The methods were validated over a range of 0.5–4 μg/spot for sumatriptan and 0.5–3 μg/spot for zolmitriptan. The proposed methods were successfully applied for the determination of the studied drugs in bulk powder and in their pharmaceutical formulations.     

Determination of Tedizolid Phosphate Using Graphene Nanocomposite Based Solid Contact Ion Selective Electrode; Green Profile Assessment by Eco-scale and GAPI Approach

Antibiotics determination plays a major role in minimizing antimicrobial resistance starting from quality control of pharmaceutical formulations to therapeutic drug monitoring. Green modified glassy carbon electrode has been developed for determination of tedizolid phosphate; new antibiotic prodrug; in presence of its active metabolite. The graphene transducer interlayer, dispersed with PVC, improved the electrode stability and standard potential reproducibility. Graphene hydrophobicity prevented the water layer formation between the sensing layers that decreased the potential drift down to 267 μV h⁻¹. Electrochemical impedance showed a low resistance value for graphene containing sensor due to its high electron transfer ability.     

Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design,synthesis, anticonvulsant evaluation,ADMET profile and molecular docking

Molecular Diversity - In view of the anticonvulsant activity reported for phthalazine derivatives as non-competitive AMPA receptor antagonists, a new series of phthalazine-1,4-diones (2–12)...     

A model for the homotopy theory of homotopy theory

We describe a category, the objects of which may be viewed as models for homotopy theories. We show that for such models, ``functors between two homotopy theories form a homotopy theory', or more precisely that the category of such models has a well-behaved internal hom-object.

     

Potentiometric ion-selective electrodes for determination of cyclopentolate hydrochloride and phenylephrine hydrochloride in their challenging ophthalmic formulation

Introduction of potentiometric ion-selective electrodes (ISEs) opened a new bright area in pharmaceutical analysis acknowledged as being an eco-friendly, simple, and energy-saving technique that is well-suited with microfabrication. In this contribution, potentiometric ISEs were employed as an alternative green analytical tool with the crucial goal of expanding the effective application of the potentiometric sensors in different disciplines of drug-stability studies and quality-control investigations. Four novel cyclopentolate hydrochloride and phenylephrine hydrochloride selective membrane sensors were constructed and evaluated. Sensors’ fabrication was achieved using potassium tetrakis (4-chlorophenyl) borate, a cationic exchanger, in a polyvinyl chloride polymeric matrix plasticized with 2-nitrophenyl octyl ether and using 2-hydroxy propyl-β-cyclodextrin as an ionophore. A comparative potentiometric study was implemented using two designs of ISEs; a conventional liquid inner contact and a glassy carbon solid-contact one. Using solid-contact ISEs, detection limit was substantially decreased and the discriminative ability in the presence of the most interfering substances was enhanced. This permits simultaneous estimation of both drugs, in spite of their similar ionic characteristics, abolishing the need for any pretreatment or separation steps in their challenging combined ophthalmic formulation as well as in rabbit aqueous humor and in the presence of their degradation products.     

Promoter Methylation of RASSF1A Gene in Egyptian Patients with Ovarian Cancer

Ovarian malignancy is diagnosed in nearly a fourth of a million women internationally every year. Methylation of RASSF1A tumor suppressor gene prompts its inactivation in diseases. In this study, the RASSF1A promoter methylation was detected by methylated-specific PCR and investigated serum RASSF1A protein level through enzyme-linked immunosorbant assay in 160 Egyptian patients with ovarian cancer and 160 healthy controls. The present work proved that there was a higher frequency of RASSF1A methylation and a decrease in its serum level in patients with ovarian cancer compared to controls as well as in the high-grade tumor patients compared to low grade ones and also in advanced ovarian tumor stage compared to early stages. Our study exhibited that RASSF1A promoter hypermethylation and its protein levels may be a reliable and sensitive tool for diagnosing and monitoring of ovarian malignancy patients.     

Reactions with 2-mercaptopyrimidines. Synthesis of some new thiazolo[3,2-a]- and triazolo[4,3-a]pyrimidines

Alkylation of 5-cyano-4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine I with methyl iodide, chloroacetic acid or 3-chloro-2,4-pentanedione, afforded the S-alkyl derivatives IIa-c. 2-Carboxymethylthio and 2-(2′,4′-dioxopentan-3-ylthio) derivatives IIb and IIc could be cyclised by acetic anhydride or polyphosphoric acid to give 6-cyano-3,5-dioxo-5H-7-phenylthiazolo[3,2-a]pyrimidine III and 2-acetyl-6-carboxamido-5H-3-methyl-7-phenylthiazolo[3,2-a]pyrimidine-5-one IX , respectively. Benzoylation of 2-hydrazinopyrimidine derivative XII , in anhydrous dioxan, afforded the N-benzoyl derivative XIII , which could be cyclised by heating in dimethylformamide to give 5-amino-6-cyano-3,7-diphenyl-s-triazolo[4,3-a]pyrimidine ( XIV ). The 2-hydrazinopyrimidine derivatives XII and XV reacted with benzoyl isothiocyanate in dioxane to yield 4-benzoylthiosemicarbazide derivatives XVI and XVII , which were converted into the 2-s-trizolopyrimidine derivatives XVIII and XIX , respectively. Also, XVI and XVII reacted with 2,4-pentanedione and 3-chloro-2,4-pentanedione to yield 2-pyrazolopyrimidine derivatives XX and XXI , respectively.     

Stability-indicating determination of meropenem in presence of its degradation product

Stability-indicative determination of meropenem (MERM) in the presence of its open-ring degradation product, the metabolite, is investigated. The degradation product has been isolated, via acid-degradation, characterized and confirmed. Selective quantification of MERM, singly in bulk form, pharmaceutical formulations and/or in the presence of its major degradate is demonstrated. The indication of stability has been undertaken under conditions likely to be expected at normal storage. Among the analytical techniques adopted for quantification are spectrophotometry [first-derivative (¹D), first-derivative of ratio spectra (¹DD) and bivariate analysis], as well as chromatography [coupled TLC-densitometry and HPLC].