BRCA1 and BRCA2 genes encode proteins that have important roles in DNA repair and act as tumor suppressors. Though the sequence and structure of the proteins produced by BRCA1 and BRCA2 are different, they have similar biological activities. Both BRCA gene products are reported to interact with the RAD51 protein, which is essential for DNA repair through homologous recombination. BRCA gene mutations are associated with an increased risk of solid tumors. Their ubiquitously expressed protein products are involved in essential cellular functions. The defect caused by BRCA gene mutations might be leveraged to develop new targeted cancer treatments. This chapter outlines that BRCA1 and BRCA2 have unique roles in the pathways leading to DNA double-strand break repair and clinical findings show that BRCA genes play a crucial role in a variety of biological processes.

A novel, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Capmatinib in human plasma and its pharmacokinetic application in rabbits. Chromatographic separation of the Capmatinib and internal standard ([ 13 CD 3 ]Capmatinib) were achieved on Phenomenex Luna C18 column (50 mm × 2 mm × 5 µm) with 0.5 ml/minute flow rate and coupled with API6000 triple quadrupole MS in multireaction monitoring mode by applying mass transitions m/z 413.15-128.05 for Capmatinib and m/z 416.20-131.01 for the internal standard. The calibration curve exhibited linearity over the concentration of 1.0-28,000.0 ng/ml for Capmatinib. The LLOQ was 1.0 ng/ml. The validated LC-MS/MS method was effectively applied for the analysis of plasma in healthy rabbits for the determination of Capmatinib. From pharmacokinetic studies, Capmatinib showed average AUC last of 12,964.14 ± 635.97 hour * ng/ml and C max of 2,537.94 ± 12.42 ng/ml in the subjects. In summary, the developed method has been successfully validated and pharmacokinetic parameters were demonstrated after oral administration of Capmatinib to healthy rabbits.

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A novel, sensitive, and specific LC-MS/MS technique was developed for the quantification of Relugolix in plasma and validated as per the regulatory guidelines. Elution of Relugolix and Canagliflozin was achieved on Inertsil C18 (150mm × 2.10mm i.d, 5.0 μm particles size) column with acetonitrile and 0.1% HCOOH as a mobile phasic system in the fraction of 90:10 with a flowrate of 0.8 mL/min. The sciex API 6000 triple quadrupole mass equipment was executed with the mode of multiple reactions and m/z 624.18/127.03 for Relugolix and m/z 445.14/267.12 for the Canagliflozin, were the optimized transitions. Relugolix exhibited a rectilinear plot in the range of 3.9 – 1500.0 ng/mL concentrations. The LC–MS/MS validated methodology was efficiently utilized for the assessment of Relugolix in the rabbit plasma. From the pharmacokinetics data, the mean of Cmax and Tmax were 42.01 ± 0.99 ng/mL and 5.922 ± 0.157, individually. Plasma conc. reduced with t1/2 of 8.28 ± 0.174. AUC0→Last value obtained was 303.437 ± 8.01 ng. h/ml, respectively. In short, the method that was produced has been successfully tested, and pharmacokinetic parameters were shown after healthy rabbits were given Relugolix orally.

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