Aim and Objective:The present study is undertaken to study the ultra structural features of muscle tissue in moderate and advanced stages of oral submucous fibrosis along with retrospective analysis of 80 cases of oral submucous fibrosis ( osmf) 0 during the period of year 2002 to 2005.Materials and Methods:Five patients with moderate and advanced stages of osmf0 were screened from outpatients department of oral diagnosis, sri Ramachandra dental college and hospital. After a detailed case history, they were subjected to incisional biopsy from an area of buccal mucosa with maximum palpable fibrotic bands.the specimens were cut into two halves, one half was fixed in 10% formalin for routine processing. Second half was fixed in 2.5% glutaraldehyde for electron microscopic examination.Results:Prospective study of muscle fibres from moderate and advanced stages of osmf0 revealed varying changes in high proportion of muscle fibres which includes, irregularity of surface of fibre,sarcolemmal foldings, reduplicated basement membrane, loss and alterations in the myofilaments, hypercontraction of myofibrils, Z line abnormalities, internal nucleus, autophagic vacuoles. These features are suggestive of muscle atrophy and necrosis.Conclusion:Within the limitations of this study, it can be concluded that the ultra structural features In moderate and advanced stages of osmf0 were best studied. These muscle changes can be manifestation of disease, atrophy being secondary to the limited functional activity of the muscles which is brought about by fibrosis or it could be essential part of the disease process itself.

<p class="Default"><strong>Objective: </strong>A simple, cost-effective and mass compatible ultra-high fast performance liquid chromatographic (Agilent-Infinity LC 1290) method has been developed and validated for the determination of potentially genotoxic impurities in dasatinib active pharmaceutical ingredients.</p><p class="Default"><strong>Methods: </strong>This method comprises the determination of three possible genotoxic impurities in dasatinib. The mobile phase is trifluoroacetic acid, acetonitrile and water with linear gradient elution curve number 6. The column used for the development and validation is zorbax RRHD eclipse plus C18 with the length of 50 mm, the internal diameter of 2.1 mm and particle size of 1.8 microns.</p><p class="Default"><strong>Results: </strong>The limit of detection of the potential genotoxic impurities are less than 0.1 µg/ml with respect to dasatinib test concentration of 1000 µg/ml. The limit of quantification of the potential genotoxic impurities is less than 0.3 µg/ml with respect to dasatinib test concentration of 1000 µg/ml.</p><p style="margin: 6pt 0cm; text-align: justify;"><strong>Conclusion: </strong>This method has been validated as per ICH guidelines Q2 (R1). These three potential mutagenic impurities are not degradant impurities of dasatinib and its only process related impurities. The method development has been approached using the QbD principle.</p>

A simple, selective and reliable LC-MS/MS method was validated for simultaneous quantitation of darolutamide diastereomers in 50 μL mouse plasma using warfarin as an internal standard (IS) as per regulatory guidelines. Plasma samples were extracted by liquid-liquid extraction and the chromatographic separation was achieved on a Chiralpak IA column with an isocratic mobile phase 5 mm ammonium acetate-absolute alcohol (20:80, v/v) at a flow rate of 1.0 mL/min. Detection and quantitation was done in multiple reaction monitoring mode following the transitions m/z 397 → 202 and 307 → 250 for darolutamide diastereomers and the IS, respectively, in the negative ionization mode. The linearity range was 100-2400 ng/mL for each diastereomer. The intra- and inter-day precisions were in the ranges of 1.78-4.20 and 4.34-14.6, and 3.63-4.74 and 4.78-5.15 for diastereomer-1 and diastereomer-2, respectively. Both diastereomers were found to be stable under different stability conditions. The validated method was applied to a pharmacokinetic study in mice. Following oral administration of darolutamide at 10 mg/kg, maximum concentration in plasma was 4189 and 726 ng/mL for diastereomer-1 and diastereomer-2, respectively. The terminal half-life was found to be ~0.50 h for both the diastereomers. The AUC was found to be 18,961 ng*h/mL for diastereomer-1 and 1340 ng*h/mL diastereomer-2.

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