Objective: Venetoclax is a selective, potent, first-in-class BCL-2 inhibitor that restores apoptosis in cancer cells and has demonstrated clinical efficacy in a variety of haematological malignancies. There is no reported evidence for its measurement in human plasma. Method: A simple, sensitive and specific high-throughput HPLC-ESI-Tandem Mass Spectrometric method was developed for the estimation of Venetoclax (VX) in human plasma using Venetoclax-D8 (VXD8) as an internal standard (IS). Chromatographic separation was performed on Zorbax SB-C18, 75 x 4.6 mm, 3.5 mm, 80 Å column with an isocratic mobile phase composed of Methanol and 5mM Ammonium acetate in the ratio of (70:30 v/v), at a flow-rate of 0.6 mL/min. The proton adducts of VX and VXD8 were detected at m/z 868.12 → 321.54 and 876.9 → 329.7 respectively, using multiple reaction monitoring (MRM) positive mode respectively. The Liquid-Liquid extraction method was used to extract the analyte and IS. Results: The method was successfully validated over linearity concentration range of 10.0-10000.0 pg/mL with the correlation coefficient (r 2) ≥ 0.9997. This method demonstrated intra and inter-day precision within 5.7 to 7.7 and 5.95 to 8.5 and % Accuracy within 96.3 to 98.7 and 98 to 100.4 %. Venetoclax was found to be stable throughout freeze-thawing cycles, bench top, postoperative stability studies. Conclusion: The method was suitable and conveniently applicable to pharmacokinetic and bioavailability studies for estimation of Venetoclax in biological matrices by HPLC-MS/MS.
The fixed dose combination of ledipasvir (LDV) and sofosbuvir (SBV) is approved by USFDA in 2014 for the treatment of Hepatitis C virus infection and is available in the form of tablets. In the present work, the principal aim is to explore orodispersible films type dosage form to impart its characteristic advantages to these poorly soluble drugs so as to improve their bioavailability and ease of administration. Solid dispersions with low viscosity grade methyl cellulose A 15-LV (MC A 15-LV) at different ratios with LDV and SBV were prepared and evaluated to check their ability in improving the solubility of the drugs. The best drug to polymer ratio was selected to develop the films, using other excipients including plasticizer and superdisintegrant. Solvent casting method was used to develop the films. Three formulation parameters were selected as independent factors viz. thickness of the film (50-150 µm), concentration of superdisintegrant (sodium starch glycolate 6-10%) and concentration of plasticizer (polyethylene glycol 400, 10-20%). Disintegration time (DT), time for 90% dissolution (T90%) of LDV and time for 90% dissolution of SBV were taken as the response variables. The experiment was designed using Box-Behnken design. Among the polymers, MC A 15-LV produced maximum solubility at 1:2 ratio. The films obtained were found to have good tensile strength and % elongation with disintegration times in the range of 43-162 sec. The T90% values for LDV and SDV were found to be in the range of 8.4-21.2 min and 7.2-18.4 respectively. All the three formulation factors were found to have significant effect on the three responses. The optimum formulation was identified at 100 µm thickness, 10% superdisintegrant and 20% plasticizer which showed DT of 89 sec with T90% values of 8.4 min and 7.2 min for LDV and SBV respectively. The rapid disintegration and dissolution of the films signified that the set objective was achieved.
As traditional drug delivery poses many disadvantages such as difficulty in consumption, the granules were opted to replace tablet dosage forms available in the market. A 23 full factorial design was employed for the formulation and characterization of the granule dosage form of oxcarbazepine. From regression equations we can assess the impact of each factor on the response further contour plots helped to pre-analyze the desired target factor values, in addition optimization process helped to analyze the values of dependent variables. Thus as of the results achieved a preferred response of flow property and drug release was obtained. In the current study, an attempt has been made to minimize possible number of experiments in the formulation of granule dosage forms. Polyvidone is a hydrophilic binder and primellose is a good disintegrate to obtain higher dissolution rate. A part, microwave assisted drying process plays a major role in achieving desired flow properties of granules.DOI: http://dx.doi.org/10.3329/icpj.v2i7.15153 International Current Pharmaceutical Journal, June 2013, 2(7): 115-118
A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of cabozantinib (CZ) in human plasma using cabozantinib-d4 (CZD4) as an internal standard (IS). Chromatographic separation was performed on Xbridge C18, 50 x 4.6 mm, 5 mm column with an isocratic mobile phase composed of 10mM Ammonium formate and Methanol in the ratio of (20:80 v/v), at a flow-rate of 0.7 mL/min. CZ and CZD4 were detected with proton adducts at m/z 502.2 → 391.1 and 506.3 → 391.2 in multiple reaction monitoring (MRM) positive mode respectively. Liquid-Liquid extraction method was used to extract the drug and IS. The method was validated over a linear concentration range of 5.0-5000.0 pg/mL with correlation coefficient (r 2) ≥ 0.9994. This method demonstrated intra and inter-day precision within 1.95 to 2.37 and 2.93 to 9.3 % and Accuracy within 101.4 to 102.4 and 99.5 to 104.8 %. Cabozantinib was found to be stable throughout freeze-thawing cycles, bench top and postoperative stability studies.
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