Background: A simple quantification technique by liquid chromatography–electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is required for regorafenib in biological matrices with bioavailability studies in healthy rabbits, when compared with reported techniques. Objective: The main aim of the research work is to develop a validated LC-ESI-MS/MS technique for the quantification of regorafenib and application to bioavailability studies in healthy rabbits. Methods: Chromatographic separation was achieved with hypersil-C18 analytical column (50mm×4.6 mm, 4µm) and a mobile phase composition of acetonitrile and 5mM ammonium acetate in the proportion of 70:30. The mobile phase was infused into the column with high pressure to get 0.7 ml/min flow rate. The total retention time of the analyte is promising when compared with the existed methods for regorafenib. Quantitation was processed by monitoring transitions of m/z -483.0/262.0 and 450.0/260.0 for regorafenib and internal standard respectively in multiple reaction monitoring. Results: The linearity equation and correlation coefficient (R2) findings were y =0.9948x+2.6624 and 0.998 respectively. The intra and inter-day precision of the developed technique was found between 1.00 – 8.50% for the QC-samples (2, 4, 240 and 480ng/ml). From bioavailability study, the drug was shown Tmax of 3.688 ± 0.754; average AUC0͢α and AUC0͢t was 6476.81 ± 259.59 and 6213.845 ± 257.892 and Cmax was found to be 676.91 ± 22.045 in healthy rabbits. Conclusion: The developed technique was validated and successfully applied in the pharmacokinetic study of drug (40 mg tablet) administered through oral route in healthy rabbits.

An accurate, specific, and robust liquid chromatography-tandem mass spectrometry technique was developed and validated for the quantification of dabrafenib in plasma samples. Internal standard and drug components were subjected to extraction by utilizing liquid-liquid extraction method by utilizing ethyl acetate. high performance liquid chromatography of reverse phase was operated with Phenomenex (50×4.60 mm, 5.0 µm) C 18 analytical column, isocratic system of mobile solvent comprised acetonitrile and formic acid (0.1%) (85:15, %V/V). Mass triple quadrupole detection system was utilized for the analysis. Electrospray ionization in the positive ionization approach method operated in multiple reactions monitoring with ionic transition of m/z 520.10-176.98, m/z 465.09-244.10 for dabrafenib, sorafenib, respectively. Rectilinear plot was processed in concentration levels of 74-2,956 ng.ml −1 and the method validation was executed as per the United States Food and Drug Administration strategies for bio analytical methods. The recovery findings obtained were more than 92.5% and the accurateness was fall in between-1.53% and 2.94% of relative error and % relative standard deviation findings were <4.65%. The high sensitiveness, better accuracy, and precision with good recovery findings for the plasma samples of a developed method prove its applicability for pharmacokinetics and bioequivalence studies.

A specific liquid chromatography-mass spectrometry/mass spectrometry spectrometric procedure for the quantitation of amprenavir drug in biological matrices was developed and validated. Chromatographic isolation was accomplished through a Zorbax C18 analytical stationary phase having the dimensions of 50 mm × 4.6 mm and particle size of 5.0 μm. Isocratic separation was processed with acetonitrile 0.1%v/v HCOOH in water and methyl alcohol in the proportion of 60:10:30 as a moveable system with a flow rate of 0.60 mL/min. Liquid-liquid extraction was carried out for drug and internal standard isolation with an ethyl acetate solvent. Parent and product ionic components were examined at m/z 506.2 → 89.1 for amprenavir and 367.1 → 350.1 for rilpivirine internal standard on the MRM (multiple reaction monitoring) mode. The linearity plot of analyte was rectilinear in the concentration over 0.15-1500 ng/mL with the correlation coefficient value of r 2 being >0.990. %relative standard deviation findings were <4.21% for intraday and interday accuracy and precision. The technique has good recoveries, and %recovery findings of LQC (low quality control), MQC(median quality control), and HQC (high quality control) solutions were 92.9%, 95.1%, and 96.4%, respectively. Amprenavir has more stability for longer time when subjected to different stability environments and the procedure was efficiently relevant to the regular investigation of amprenavir analyte in the biological matrix.

No abstract