A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of Afatinib in human plasma using Cabozantinib as an internal standard (IS). Chromatographic separation was performed on Water X Bridge c18 2.1x100 column with an isocratic mobile phase composed of acetonitrile and 0.2% Ammonia in water in the ratio of (70:30 v/v), at a flow rate of 0.250mL/min. Afatinib and Cabozantinib were detected with parent ions at m/z 486.36 to 370.90 and the daughter mass was found to be 381.45 to 304.93 in multiple reaction monitoring (MRM) positive mode respectively. The protein precipitation method was used to extract the drug and IS. The method was validated over a linear concentration range of 2.0-1000.0 ng/mL with a correlation coefficient (r2) ≥ 0. 9994. This method demonstrated Intra and inter-day Precision within 0.3 to 2.5 and 0.4 to 3.9 % and Accuracy from 96.55 to 105.45 and 95.26 to 110.6%. Afatinib was found to be stable throughout Long-term stability studies, benchtop, and postoperative stability studies.
Objective: Pyrimidine heterocycles possessing hydroxy group has a unique place in medicinal chemistry and also plays a key role in biological processes. In the biological functions at cellular level pyrimidine plays imperative roles which lead the researchers to design a variety of its derivatives. The aim of the present study was to synthesize the novel set of 4-(4-fluoro-3-methylphenyl)-6-(substituted aryl)-1,6-dihydropyrimidin-2-ol derivatives. These compounds were screened for their analgesic and anti-inflammatory activities. Methods: A novel series of 4-(4-fluoro-3-methylphenyl)-6-(substituted aryl)-1,6-dihydro pyrimidin-2-ol derivatives were furnished in two steps starting from 4-fluoro-3-methyl acetophenone through chalcone formation. Human red blood cell membrane stabilization method and carrageenan-induced rat paw edema test were performed for screening in vitro and in vivo anti-inflammatory activity, respectively. Tail-flick technique was performed for screening analgesic activity. Results: All the synthesized 4-(4-fluoro-3-methylphenyl)-6-(substituted aryl)-1,6-dihydro pyrimidin-2-ol derivatives were characterized by Fourier-transform infrared spectroscopy,1H nuclear magnetic resonance, mass spectroscopy, and bases of elemental analysis. The result of biological screening revealed that many of the new derivatives were endowed with improved anti-inflammatory and analgesic activities. Conclusion: Nature of the substituent played a major role in anti-inflammatory and analgesic activities. The pyrimidine derivative with chlorophenyl substitution exhibited potent anti-inflammatory and analgesic activities. From the results, it was concluded that 6-(4-chlorophenyl)-4-(4-fluoro-3- methyl phenyl)-1,6-dihydropyrimidin-2-ol was the most active compound.
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