Structural Elucidation of Alkali Degradation Impurities of Favipiravir from the Oral Suspension: UPLC-TQ-ESI-MS/MS and NMR

A novel stability-indicating, reversed-phase, high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination of favipiravir in an oral suspension. The effective separation of favipiravir and its degradation products was achieved on a Zorbax Eclipse Plus C18 column (5 μm particle size, 150 mm length × 4.6 mm diameter). The mobile phase was prepared by mixing 5 mM of phosphate buffer (pH 3.5) and methanol in a 75:25 v/v ratio delivered at a 1.0 mL/min flow rate. The eluents were monitored using a photodiode array detector at a wavelength of 322 nm. The stability-indicating nature of this method was evaluated by performing force degradation studies under various stress conditions, such as acidic, alkali, oxidative, thermal, and photolytic degradation. Significant degradation was observed during the alkali stress degradation condition. The degradation products generated during various stress conditions were well separated from the favipiravir peak. In addition, the major degradation product formed under alkali stress conditions was identified using UPLC-ESI-TQ-MS/MS and NMR. Method validation was performed according to the ICH Q2 (R1) guideline requirements. The developed method is simple, accurate, robust, and reliable for routine quality control analysis of favipiravir oral suspensions.     

Separation of sulfonamides by capillary electrochromatography

Summary The dual separation mechanism exhibited by capillary electrochromatography is demonstrated by the simultaneous separation of sulfonamides as charged and neutral species over a pH range of 2.5 to 6.9. The neutral sulfonamides were separated according to the difference in their hydrophobicities while charged components were separated by the differences in their electrophoretic mobilities. The limitation of capillary electrochromatography for acidic components was also examined.     

On the hull-kernel and inverse topologies as frames

We consider some frame-theoretic properties of the hull-kernel and the inverse topologies on the set of minimal prime ideals of an algebraic frame with the finite intersection property on its compact elements. Denote by Alg _do the subcategory of Frm consisting of such frames together with dense onto coherent maps. We construct a functor ${{\sf T} : {\bf Alg}_{\rm do} \rightarrow {\bf Frm}}$ T : Alg do → Frm and a natural transformation ${\tau : {\sf E} \rightarrow {\sf T}}$ τ : E → T , where E is the inclusion functor from Alg _do to Frm.     

A Simple and Rapid Stability Indicating LC Determination of Ciprofloxacin Hydrochloride as a Bulk Drug and from Formulations

The present research work discusses the development of a stability indicating reversed phase LC method for determination of ciprofloxacin hydrochloride as a bulk drug and from formulations. The mobile phase selected was water-acetonitrile-triethylamine 75:25:0.1 (v/v/v) adjusted to pH 4.0 with o-phosphoric acid. The calibration curve of the drug was linear in the range 0.25–15 μg mL^?1. The method was accurate and precise with limits of detection and quantitation of 8.01 and 26.7 ng, respectively. Mean percent recovery was 100.71%. The method was used for analysis of ciprofloxacin hydrochloride from pharmaceutical formulations in the presence of its degradation products and commonly used excipients.     

Interaction of chlorin p6 with bovine serum albumin and photodynamic oxidation of protein

The binding of chlorin p6, a photosensitizer having basic tetrapyrrole structure, to bovine serum albumin (BSA) and oxidation of the protein following photodynamic treatment is studied. The Stern-Volmer plot indicates that binding of chlorin p6 to BSA was of single class. Binding parameters, binding association constant and number of binding sites, were found to be 1.62+/-0.27 x 10(5)M(-1) and 1.086+/-.019, respectively. Photodynamic oxidation of protein was studied by (i) loss of intrinsic fluorescence of protein, (ii) protein carbonyl formation, (iii) protein hydroperoxide (iv) formation of TCA soluble amino groups and (v) SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Intrinsic protein fluorescence was observed to decrease almost linearly as a function of irradiation time at a fixed concentration of chlorin p6 and with increasing concentration of chlorin p6 at fixed time of irradiation. Protein carbonyl and hydroperoxide formation was found to increase with increasing photodynamic treatment. No significant increase in 5% TCA soluble amino groups was observed. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) reveals that photodynamic treatment of BSA in presence of chlorin p6, rose bengal and riboflavin causes non-specific fragmentation of protein. Photodynamic carbonyl formation by chlorin p6 was not inhibited by sodium formate (100 mM) or mannitol (25 mM) but was significantly inhibited by sodium azide (2 mM). Protein carbonyl formation increased almost 90% when H2O was replaced by D2O. The results show that chlorin p6 induced photodynamic oxidation of BSA was mainly mediated by singlet oxygen.     

A supersonic molecular beam study of the reaction of tetrakis(dimethylamido)titanium with self-assembled alkyltrichlorosilane monolayers

The reaction of a transition metal coordination complex, Ti[N(CH(3))(2)](4), with self-assembled monolayers (SAMs) possessing-OH, -NH(2), and -CH(3) terminations has been examined using supersonic molecular beam techniques. The emphasis here is on how the reaction probability varies with incident kinetic energy (E(i)=0.4-2.07 eV) and angle of incidence (theta(i)=0 degrees -60 degrees ). The most reactive surface is the substrate underlying the SAMs-SiO(2) with a high density of -OH(a) (>5 x 10(14) cm(-2)), "chemical oxide." On chemical oxide, the dynamics of adsorption are well described by trapping, precursor-mediated adsorption, and the initial probability of adsorption depends only weakly on E(i) and theta(i). The dependence of the reaction probability on substrate temperature is well described by a model involving an intrinsic precursor state, where the barrier for dissociation is approximately 0.2-0.5 eV below the vacuum level. Reaction with the SAMs is more complicated. On the SAM with the unreactive, -CH(3), termination, reactivity decreases continuously with increasing E(i) while increasing with increasing theta(i). The data are best interpreted by a model where the Ti[N(CH(3))(2)](4) must first be trapped on the surface, followed by diffusion through the SAM and reaction at the SAMSiO(2) interface with residual -OH(a). This process is not activated by E(i) and most likely occurs in defective areas of the SAM. On the SAMs with reactive end groups, the situation is quite different. On both the-OH and -NH(2) SAMs, the reaction with the Ti[N(CH(3))(2)](4) as a function of E(i) passes through a minimum near E(i) approximately 1.0 eV. Two explanations for this intriguing finding are made-one involves the participation of a direct dissociation channel at sufficiently high E(i). A second explanation involves a new mechanism for trapping, which could be termed penetration facilitated trapping, where the Ti[N(CH(3))(2)](4) penetrates the near surface layers, a process that is activated as the molecules in the SAM must be displaced from their equilibrium positions.     

On openness and surjectivity of lifted frame homomorphisms

Given a completely regular frame L, let, as usual, βL, λL and υL denote, respectively, the Stone-?ech compactification, the universal Lindelöfication and the Hewitt realcompactification of L. Let γ denote any of the functors β, λ or υ. It is well known that any frame homomorphism h:L→M has a unique “lift” to a frame homomorphism hγ:γL→γM such that σM⋅hγ=h⋅σL, where the σ-maps are effected by join. We find a condition on h such that if h satisfies it, then h is open iff its lift hγ is open. Furthermore, the same condition ensures that hγ is nearly open iff h is nearly open. This latter result is, in fact, a special case of a more general phenomenon. In the last part of the paper we investigate when hυ is surjective. The instances when hβ or hλ is surjective are known. It turns out that the surjectivity of the lifted map hυ:υL→υM captures Blair's notion of υ-embedding in the sense that a subspace S of a Tychonoff space X is υ-embedded iff the lifted map υ(Oi):υ(OX)→υ(OS) is surjective, where i:S→X is the subspace embedding.     

A novel dual-nano assisted synthesis of symmetrical disulfides from aryl/alkyl halides

Here, we have reported a novel approach towards dual-nano assisted synthesis of disulfides from coupling of alkyl/aryl halides and sulfur nanoparticles. The indium oxide nanoparticles as catalyst expedite the conversion and sulfur nanoparticle notably enhances the miscibility, providing a faster, high yielding and cost-effective process in ethanol-water system. The method has synthetic advantages in terms of mild reaction framework, catalyst regeneration, and absence of any sulfide or polysulfide linkage as by-product leading to a column free synthesis. A variety of alkyl, aryl and heteroaryl symmetrical disulfides are obtained in good to excellent yields up to exceeding 98%.     

Growth of first generation dendrons on SiO2: controlling chemisorption of transition metal coordination complexes

We have investigated the growth of first generation branched polyamidoamine dendrons on silicon dioxide as a way to tailor and control the subsequent chemisorption of transition metal coordination complexes. Beginning with straight-chain alkyl, amine-terminated self-assembled monolayers as anchors, we find that the efficiency of the dendritic branching step depends on the length of the anchor, it being nearly perfect on a 12-carbon chain anchor. The reaction of these layers, both the anchor layers and the first generation dendrons, with Ta[N(CH3)2]5 and Ti[N(CH3)2]4 have been examined in ultrahigh vacuum using X-ray photoelectron spectroscopy. We find that the saturation coverage increases with the density of terminal -NH2 groups; thus, the branching step has effectively amplified the chemisorptive capacity of the surface. Concerning the spatial extent of reaction we find that it depends on the thickness and structure of the organic layer. The thinnest layer cannot prevent penetration of the metal complex to the organic/SiO2 interface, where it can react with residual -OH, whereas, on the longer straight chain anchor, reaction occurs exclusively at the terminal -NH2 group. On the branched dendrons, the situation is more complex, and reaction occurs not only with the terminal -NH2 group but also likely with functional groups, such as -NH-(C=O)-, on the backbone of the branched dendron.     

5-Aminolevulinic acid-induced protoporphyrin-IX accumulation and associated phototoxicity in macrophages and oral cancer cell lines

Studies were carried out on 5-aminolevulinic acid (ALA)-induced protoporphyrin (PpIX) synthesis in mice peritoneal macrophages and two human oral squamous cell carcinoma (OSCC) cell lines NT8e and 4451. Cells were treated with 200 microg/ml ALA for 15 h and PpIX accumulation was monitored by spectrofluorometry and phototoxicity to red light (630+/-20 nm) was measured by MTT assay. PpIX accumulation was higher in macrophages as compared to OSCC cells under both normal serum concentration (10%) and conditions of serum depletion. The results on phototoxicity measurements correlated well with the levels of PpIX accumulation in both macrophages and cancer cells. While red light caused 20% phototoxicity in macrophages, no phototoxicity was seen in 4451 cells at 10% serum. Decrease in serum concentration to 5% and 1% led to higher phototoxicity corresponding to 40% and 70% in macrophages and 10% and 15% in 4451 cells. Similar results were obtained in NT8e cell line. Propidium iodide staining followed by fluorescence microscopic observations on photodynamically treated co-culture of murine or human macrophages and cancer cells showed selective damage to macrophages. These results suggest that in OSCC, macrophages would contribute more to tumor PpIX level than tumor cells themselves and PDT may lead to selective killing of macrophages at the site of treatment. Since macrophages are responsible for production and secretion of various tumor growth mediators, the effect of selective macrophage killing on the outcome of PDT would be significant.