BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF ENTRECTINIB IN RAT PLASMA BY LIQUID CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY

Objective: The objective of the study was to develop and validate the bioanalytical liquid chromatography–mass spectrometry (LCMS/MS) method for the estimation of entrectinib in bulk and pharmaceutical drugs in rat plasma. Methods: Chromatographic separation of entrectinib with D4-entrectinib as internal standard (IS) was achieved using Waters Alliance high-performance liquid chromatography system, quaternary gradient pump of e2695, using Luna, 250×4.6 mm, 5 μm column and the mobile phase containing 0.1% formic acid and acetonitrile (ACN) within the ratio of 70:30% v/v. The flow was 1.0 ml/min; detection was carried out by absorption at 294 nm using a photodiode array detector at ambient temperature. Results: The peak of entrectinib was eluted at retention times of 5.225 min. The multiple reaction monitoring was 560.6/475.1 (m/z) for entrectinib and 580.6/496.3 (m/z) for IS entrectinib (D4). The linearity range was 1–20 ng/ml with a regression coefficient of 0.999. % relative standard deviation of peak areas of all measurements always <2.0. Conclusion: The method was successfully validated and it had been found to be within limits for accuracy, precision, and linearity and it is stable under analytical conditions used

Permian Palynoflora from Lower Gondwana Sediments of Godavari Valley Coalfield, Andhra Pradesh, South India

Palynological investigation of Lower Gondwana sediments of Goutham Khani Open Cast Mine (GKOCM) from Kothagudem sub basin of Godavari Valley Coalfield, Andhra Pradesh of Peninsular India have revealed two palynoassemblages are related to Early Permian (Barakar Formation). Palynoassemblage – A abundantly occurrence of Scheuringipollenites along with other common taxa like Parasaccites, Ibisporites, Primuspollenites, Sulcatisporites, Rhizomaspora, Densipollenites and Corisaccites and Palynoassemblage – B dominated by Scheuringipollenites along with sub dominance of Faunipollenites, Striatopodocarpites, Parasaccites, Striatites, Tiwariasporis, Rhizomaspora, Verticipollenites, Platysaccus, Primuspollenites, Lunatisporites, Latosporites, Ibisporites and Distriatites. The above demarcated palynoassemblages are applied to correlate with other horizons of Lower Gondwana deposits of India and also to fix the relative age for the sediments under investigation. Key words? Permian Age, Lower Gondwana, Palynoassemblage, Godavari Valley Coalfield, Sothern India

Biological relationship of Bean common mosaic virus (BCMV) infecting cowpea with leguminous plant species

Bean common mosaic virus (BCMV) associated with cowpea mechanically inoculated to different legumi-nous plants. Out of nineteen including cowpea Var.C-152, the virus was easily transferred to ten different legumi-nous hosts. All other hosts assessed for the presence of BCMV were found to be uninfected. The number of days taken for symptom expression and symptoms were varied within plant species. Pole bean expressed mosaic symp-tom after long incubation period (15-18 days) whereas, shorter incubation period was observed in common bean and rice bean (7- 10 days). BCMV produced chlorosis, mosaic, leaf distortion, puckering, vein banding, vein clearing and vein netting on cowpea(C-152). A typical virus symptom, mosaic was observed in green gram, common bean, lime bean, rice bean and yard long bean, whereas, leaf rolling and leaf distortion was observed in black gram, pole bean and snap bean. The virus-host relationship was confirmed by back inoculation test to C. amaranticolor. Further symptomatic plants were subjected for Reverse Transcriptase polymerase chain reaction (RT-PCR) for molecular confirmation using BCMV coat protein (CP) specific primer pair. A PCR fragment size of 439bp was amplified for the symptomatic plants. The results generated indicated the ability of a plant to support virus expression and host speci-ficity of BMCV within the leguminous plant species

Strengthening magnesium by design: integrating alloying and dynamic processing

Magnesium (Mg) has the lowest density of all structural metals and has excellent potential for wide use in structural applications. While pure Mg has inferior mechanical properties; the addition of further elements at various concentrations has produced alloys with enhanced mechanical performance and corrosion resistance. An important consequence of adding such elements is that the saturated Mg matrix can locally decompose to form solute clusters and intermetallic particles, often referred to as precipitates. Controlling the shape, number density, volume fraction, and spatial distribution of solute clusters and precipitates significantly impacts the alloy's plastic response. Conversely, plastic deformation during thermomechanical processing can dramatically impact solute clustering and precipitation. In this paper, we first discuss how solute atoms, solute clusters, and precipitates can improve the mechanical properties of Mg alloys. We do so by primarily comparing three alloy systems: Mg-Al, Mg-Zn, and Mg-Y-based alloys. In the second part, we provide strategies for optimizing such microstructures by controlling nucleation and growth of solute clusters and precipitates during thermomechanical processing. In the third part, we briefly highlight how one can enable inverse design of Mg alloys by a more robust Integrated Computational Materials Design (ICMD) approach

Rapid Quantification of Dynamic and Spall Strength of Metals Across Strain Rates

The response of metals and their microstructures under extreme dynamic conditions can be markedly different from that under quasistatic conditions. Traditionally, high strain rates and shock stresses are measured using cumbersome and expensive methods such as the Kolsky bar or large spall experiments. These methods are low throughput and do not facilitate high-fidelity microstructure-property linkages. In this work, we combine two powerful small-scale testing methods, custom nanoindentation, and laser-driven micro-flyer shock, to measure the dynamic and spall strength of metals. The nanoindentation system is configured to test samples from quasistatic to dynamic strain rate regimes (10$^{-3}$ s$^{-1}$ to 10$^{+4}$ s$^{-1}$). The laser-driven micro-flyer shock system can test samples through impact loading between 10$^{+5}$ s$^{-1}$ to 10$^{+7}$ s$^{-1}$ strain rates, triggering spall failure. The model material used for testing is Magnesium alloys, which are lightweight, possess high-specific strengths and have historically been challenging to design and strengthen due to their mechanical anisotropy. Here, we modulate their microstructure by adding or removing precipitates to demonstrate interesting upticks in strain rate sensitivity and evolution of dynamic strength. At high shock loading rates, we unravel an interesting paradigm where the spall strength of these materials converges, but the failure mechanisms are markedly different. Peak aging, considered to be a standard method to strengthen metallic alloys, causes catastrophic failure, faring much worse than solutionized alloys. Our high throughput testing framework not only quantifies strength but also teases out unexplored failure mechanisms at extreme strain rates, providing valuable insights for the rapid design and improvement of metals for extreme environments

Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations

Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precise needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevant needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21–30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and separately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload

The Gingers of the north coastal Andhra Pradesh, India

The north coastal Andhra Pradesh is one of the important agro-climatic zones of Andhra Pradesh with the high altitude hill zones. Forest range is considered as a basic unit in which harbours good patches of vegetation. Some important study areas are Chintapally, Narsipatnam, Anantagiri, Araku, Kurupam, Gummalakshmipuram, Parvathipuram, Salur and Palakonda. As zingibers are shade loving plants, they mostly grow in damp and humid shady places. Some species can fully expose to the sun, and grow on high elevation. Very few species cultivated in plain areas for the commercial and domestic purpose (Ginger, Turmeric and Ornamentals etc.). North coastal Andhra Pradesh covers the 20 percent of the forest area (6,51,537 ha), with rich sources of flora and fauna. Zingibers possess great medicinal properties like expectorant, acrid, aphrodisiac, thermogenic, febrifuge, appetiser, carminative, antihelmintic etc. They are useful in vitiated conditions of vata, pitta and kapha, respiratory diseases, digestive complaints, and Skin diseases. Because of the great medicinal properties of zingibers, they are widely used by the people from all parts of the world, and also pharmacological studies are extensively conducted on these plants

Comparative Studies on Nutritional and Phytochemical Composition of Three Milky Mushroom Varieties

Milky mushroom (Calocybe indica P&C) is a tropical potentially new species gaining popularity and demand by the mushroom growers especially in South India.As biochemical composition of milky mushrooms are influenced by the growing environmental conditions, research pertaining to these aspects is very meagre and also to compare the nutritional and biochemical composition of three milky mushroom species so that the best species can be selected by the growers, hence the present research work has been taken up to estimate the concentration of proteins, carbohydrates and phytochemical compounds like phenols, flavonoids, alkaloids and tannins in three varieties of milky mushrooms namely Calocybe indica, Calocybe gambosa and APK-2 in Mushroom Cultivation Scheme, Department of Plant Pathology, Hyderabad. The results revealed the presence of highest protein and carbohydrates content in Calocybe indica (15.9g, 2.7g) followed by APK-2 (11.2g and 2.1g) and C. gambosa (10.0g and 1.6g) and highest fats in APK-2 (2.0g), followed by C. gambosa(1.4g) and least in C. indica (1.3g) respectively. The secondary metabolites phytochemicals like phenols and tannins were highest content in C. indica (2.3 gm, 1.9mg) followed by C. gambosa (2.2gm, 1.6 mg) and next followed by APK-2 (2.1 gm, 1.5mg). Highest flavonoid content was recorded in C. indica and APK-2 of 1.5mg and least was recorded in C. gambosa of 1.4mg. Highest content of alkaloid was recorded in C. indica of 1.8mg, followed by APK-2 (1.6mg) and C. gambosa (1.5mg)

Amorphous solid dispersions of ritonavir by melt-quenching: A quality by design approach

Ritonavir is crystalline solid which is very slightly soluble in water yet having high dose. This condition necessitates enhancement of solubility before developing into dosage forms. Melt-quenching is recently exploring technique for developing amorphous solid dispersions (ASDs) for crystalline drugs to with a hydrophilic carrier to enhance solubility. ASDs have a drawback of poor thermodynamic stability which needs to be considered. The current work was aimed to develop ASDs for Ritonavir with improved solubility yet thermodynamically stable. Quality by design (QbD) was employed to elucidate the effects of the carrier, plasticizer and cooling temperature on the solubility and stability of the prepared ASDs. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) analysis were performed to investigate the physical state of Ritonavir and the stability of the ASDs upon storage. These results illustrated the effects of the factors on the solubility and stability were significant at p< 0.05. Statistical optimization was performed to identify the best combination of the factors to obtain ASDs with maximum solubility and stability. ASDs prepared with Soluplus as carrier at 50% w/w, Poloxamer 188 as plasticizer 15% w/w at6.81oC temperature were found to have desired solubility and stability