A robust, consistent, straightforward, swift, and precise liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was tailored for the bioanalytical analysis of ripretinib, with bosutinib serving as the comparative standard. This article provides a synopsis of recent developments in bioanalytical LC-MS/MS techniques utilizing a phenyl column (150x4.6 mm, 3.5 μ) and an eluting agent composed of ammonium formate at a pH of 2.5, which was altered in a 50:50 ratio with formic acid and acetonitrile. The chromatogram was utilized to analyse ripretinib, and the MS detector was equipped with electrospray ionization (ESI) method functioning in positive ionization conditions with multiple reactions monitoring (MRM). This allowed for the recording of transition m/z values of 531.4465→170.9638 for ripretinib and 511.4230 → 160.7133 for BTB. In the chromatographic analysis, ripretinib was retained for approximately 2.433 minutes, whereas BTB was retained for around 3.608 minutes. The validity of the approach extends across a linearity scale of 5 to 100 ng/mL for ripretinib, boasting a correlation index of 0.9999. In the realm of biological matrices, the extraction procedure employing the protein precipitation technique yields recovery rates of 99.6, 99.2, and 98% at the lower, middle, and higher quality control levels, respectively. The obtained results for accuracy, precision, matrix effect, and stability were determined to be within the acceptable range. To observe the investigated analyte in bodily fluids, pharmacokinetic studies yielded key parameters, including a half-life of 10 hours and a time to reach a maximum drug level of 4 hours. This thorough assessment affirms that the method satisfies rigorous criteria for system suitability and specificity well within predefined acceptance limits. Such performance positions it as an indispensable asset in the realm of bioanalysis, significantly broadening its clinical applicability.
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