This study involved the identification and characterization of ponatinib by LC-MS/MS. Additionally ponatinib reactive metabolites were also investigated using KCN as a trapping agent, showing the formation of four reactive cyano adducts.
For the first time, a capillary electrophoretic (CE) method with sample stacking induced by a reverse migrating pseudostationary phase (SRMP) technique has been developed and validated for sensitive determination of phenobarbital (PB) and its p-hydroxyphenobarbital (PHPB) metabolite in rat urine samples. Separation and determination were optimized on a fused-silica capillary with a total length of 50 cm (effective length 40 cm) and 75 μm ID. The microemulsion background electrolyte consisted of 0.8% (v/v) ethyl acetate, 6.6% (v/v) butan-2-ol, 1.0% (v/v) acetonitrile, 2.0% (w/v) sodium n-dodecyl sulfate (SDS), and 89.6% (v/v) of 7.5 mM ammonium formate at pH 8. When this preconcentration technique was used, the sample stacking and the separation processes took place successively with changing the voltage with an intermediate polarity switching step. For practical application, a solid-phase extraction (SPE), C(18) sorbent with n-hexane/ethyl acetate (1 : 1%, v/v) as the elution solvent was used for sample purification and concentration. The SPE method gave good extraction yields for all the analytes, with absolute recovery values of 96.9% and 99.1% for PB and PHPB, respectively. The regression equations for PB and PHPB showed excellent linearity over a concentration range of 55-1386 ng mL(-1) for PB and PHPB (r = 0.998). The developed microemulsion electrokinetic capillary chromatography (MEEKC) method for separation of the studied compounds with SRMP as the electrophoretic preconcentration technique allowed detection limits in urine samples at 16.8 ng mL(-1) for PB and PHPB which are 15-fold lower than the reported CE method in the literature. The precision results, expressed by the intra-day and inter-day relative standard deviation (RSD) values range from 3.6 to 7.1% (repeatability) and from 3.2 to 7.2% (intermediate precision) for PB and PHPB, respectively, which were in line with Food and Drug Administration (FDA) criteria.
A reliable, high-throughput and sensitive LC-MS/MS procedure was developed and validated for the determination of five tyrosine kinase inhibitors in human plasma. Following their extraction from human plasma, samples were eluted on a RP Luna®-PFP 100 Å column using a mobile phase system composed of acetonitrile and 0.01 m ammonium formate in water (pH ~4.1) with a ratio of (50:50, v/v) flowing at 0.3 mL min . The mass spectrometer was operating with electrospray ionization in the positive ion multiple reaction monitoring mode. The proposed methodology resulted in linear calibration plots with correlation coefficients values of r = 0.9995-0.9999 from concentration ranges of 2.5-100 ng mL for imatinib, 5.0-100 ng mL for sorafenib, tofacitinib and afatinib, and 1.0-100 ng mL for cabozantinib. The procedure was validated in terms of its specificity, limit of detection (0.32-1.71 ng mL ), lower limit of quantification (0.97-5.07 ng mL ), intra- and inter assay accuracy (-3.83 to +2.40%) and precision (<3.37%), matrix effect and recovery and stability. Our results demonstrated that the proposed method is highly reliable for routine quantification of the investigated tyrosine kinase inhibitors in human plasma and can be efficiently applied in the rapid and sensitive analysis of their clinical samples.
Solvent-free Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes (aryl aldehydes) using solid NaOH (20 mol%) and applying a grinding technique were studied. Quantitative yields (96–98%) of α,α'-bis-(substituted-benzylidene)cycloalkanones were obtained. Aliphatic aldehydes also provided α,α'-bis-(substituted-alkylidene)cycloalkanones in very good yields with minor amounts of α-(substituted-alkylidene)cycloalkanones. The catalytic performance of solid NaOH was examined. The molar ratio of NaOH was optimized. The catalytic effect of solid NaOH was also evaluated by comparing it with KOH, NaOAc, and NH4OAc and it turns out that 20 mol% of solid NaOH was good enough to catalyze the Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes. Additionally, the regioselectivity of the Claisen-Schmidt reaction of acetone with benzaldehyde was examined. Using the same method, we could synthesize the corresponding bis-benzylidene- and mono-benzylideneacetone separately in 98% and 96% yields, respectively.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.