ANALYTICAL QUALITY BY DESIGN APPROACH IN RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF DUVELISIB

Objective: A simple, accurate, and robust RP-HPLC method was developed and validated for the estimation of Duvelisib using analytical quality by design approach. Methods: The critical method parameters (CMP) were systematically optimized using box-Behnken design (BBD). The CMP’s selected were % organic phase composition, column temperature, and flow rate. The critical quality attributes investigated were retention time and theoretical plates. Results: Chromatographic separation was accomplished on Agilent Zorbax Eclipse C18 (150×4.6 mm, 5 μm) column. The optimized and predicted data from Design Expert software consist of mobile phase 0.1 % orthophosphoric acid (46.3%): Acetonitrile (53.7%), pumped at a flow rate of 0.91 ml/min at 32.6°C gave the highest desirability function of 1. The retention time of the drug was found to be 2.85 min. The developed method was validated as per the ICH Q2 (R1) guidelines. Conclusion: Based on the analysis of variance values, the selected models were found to be significant with p<0.05. The results of the validation parameters were within the acceptable limit. The stability of the drug was examined under different stress conditions forcibly and significant degradation was found in acidic condition

Analytical Method Development and Validation of RP-HPLC Method for the Determination of Gemcitabine in Bulk and Pharmaceutical Dosage Forms

ABSTRACT A rapid and sensitive high performance liquid chromatographic method was developed for the estimation of Gemcitabine in bulk and pharmaceutical dosage forms. Gemcitabine was chromatographed on a Zorbax R X C 8 , (250mm× 4.6mm, 5µ) using a mobile phase consisting of phosphate buffer (pH 3.0) and methanol in the ratio of 85:15 v/v. The flow rate was maintained at 1.2 ml/min and eluents were detected at 275 nm. The retention time of Gemcitabine was found to be 11.78 min. The proposed method was validated by determining accuracy, precision, specificity and system suitability parameters. Linearity was observed in the range of 25-150 µg/ml. The mean recovery of 100.0±0.32 of the drug was indicating high level of accuracy of the method. Due to its simplicity, accuracy and high precision the proposed HPLC method was found to be appropriate for the estimation of Gemcitabine in bulk and pharmaceutical dosage forms

Primary gastrointestinal mucormycosis in an immunocompetent person

In the past decade, mucormycosis has emerged as an important lethal infection in diabetics and other immunocompromised hosts. Rhinosinusitis, pansinusitis, rhino-orbital and rhinocerebral are the common classical manifestations of mucormycosis. However, primary gastrointestinal (GI) mucormycosis is an uncommon disease associated with a high mortality rate. Stomach is the most common site involved in GI mucormycosis. Reported cases of GI mucormycosis in an immunocompetent host are very few in the literature. Here we present a case of a young male with fungal sepsis secondary to GI mucormycosis in an immunocompetent person

Plasmablastic Myeloma- A Diagnostic Dilemma

Plasmablastic neoplasms comprise various haematolymphoid tumours with plasmablastic morphology which includes Plasmablastic Myeloma (PBM) and Plasmablastic Lymphoma (PBL). Distinguishing these two entities remains a major diagnostic challenge. In view of Epstein Barr Virus (EBV)-Encoded RNA (EBER) negativity, Human Immunodeficiency Virus (HIV) negativity, high Serum Free Light Chain (SFLC) assay and absence of hypermetabolic lymphadenopathy, a final diagnosis of PBM was made. This report is about a 55-year-old lady who presented with fatigue, significant loss of weight, and appetite. She had mild enlargement of the liver, spleen and no significant lymphadenopathy. There were atypical cells in peripheral blood. Bone marrow evaluation showed 51% atypical mononuclear cells. Flow cytometry was negative for acute leukaemia diagnostic markers. Immunohistochemistry (IHC) on the bone marrow biopsy revealed positivity for Cluster of Differentiation (CD) 138, Multiple Myeloma 1 (MUM1) with kappa light chain restriction and negative for EBER. The free light chain showed a kappa:lambda light chain ratio of 28,885 (0.26-1.65). The diagnosis of PBM was made and she was started on a daratumumab-based immunotherapy regimen. She achieved complete remission after induction with Measurable Residual Disease (MRD) <0.01%. She is presently doing well on follow-up with the disease in remission status