Capmatinib (CMB) monitoring in biological fluids is critical for evaluating its pharmacokinetics, optimizing dosing, and minimizing toxicity. Accurate measurement is essential for ensuring therapeutic efficacy, enabling personalized treatment, and preventing adverse effects. Given the variability in patient metabolism and excretion, regular monitoring helps maintain CMB levels within the therapeutic range, improving treatment outcomes and minimizing the risk of drug resistance. This work presents an economical and energy-efficient strategy for preparing highly luminescent nitrogen-doped carbon dots (NCDs), employing 2,5-dihydroxy-1,4-benzoquinone alongside triethylenetetramine. The synthesized NCDs demonstrated excellent photostability and a high fluorescence quantum yield of 38.72%. Upon the addition of CMB, concentration-dependent fluorescence quenching was observed at 515 nm, which was attributed to the inner filter effect (IFE), with LOD of 3.6 nM. The NCDs exhibited high selectivity in detecting CMB, with minimal cross-reactivity from simultaneously present compounds. Recovery studies in real biological samples yielded rates between 97.4% and 105.3%, and RSDs were consistently below 4.11%. These results demonstrate the method's precision, reproducibility, and potential for reliable CMB detection in complex biological matrices.

A novel disposable ultrasensitive sensor based on nanosized ceria uniformly loaded carbon nanofiber nanoceramic film wrapped on pencil graphite rods for electrocatalytic monitoring of a tyrosine kinase inhibitor capmatinib

First electrochemical nanosensor for ultrasensitive quantification of MET inhibitor, capmatinib based on carbon nanofiber networks incorporated with hybrid nanofiller nanogold-loaded porous acetylene black

In the current study, the potential interaction mechanisms between capmatinib (CAP), a selective tyrosine kinase inhibitor, and calf thymus double-stranded DNA (ds-DNA) were evaluated. In this research, we construct an amplified electrochemical platform based on a disposable pencil graphite electrode (PGE) modified with nanostructured CeO2 decorated carbon nanofiber ceramic film (CeNPs@CNF-CF) for monitoring CAP-dsDNA interaction at physiological pH. The morphology and structure of the obtained CeNPs@CNF nanocomposite were characterized. The CeNPs@CNF-CF/PGE was characterized by scanning electron microscopy (SEM). The CAP-dsDNA interaction was examined using cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques. Voltammetric experiments were conducted using CeNPs@CNF-CF/PGE. The interaction of CAP with dsDNA was investigated after applying different incubation times. The addition of dsDNA to the CAP solution decreased the peak currents of the latter and led to a negative shift in peak potentials, suggesting that the electrostatic type of interaction is the most likely to occur. SWV was employed to quantify dsDNA, demonstrating excellent sensitivity (LOD = 5 × 10-8 M). The binding constant (K b) of CAP and dsDNA was calculated to be 4.54 ± 0.18 × 104 M-1 using SW voltammetric data.

Capmatinib (CMB) is an orally bioavailable mesenchymal–epithelial transition (MET) inhibitor approved by the US-FDA to treat metastatic non-small cell lung cancer (NSCLC) patients, with MET exon 14 skipping mutation. The current study aimed to establish a specific, rapid, and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analytical method for quantifying CMB in human liver microsomes (HLMs), with therapeutic implications for assessing metabolic stability. Validation of the UPLC-MS/MS analytical method in the HLMs was performed using selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, stability, and matrix effects according to the guidelines for bio-analytical method validation of the US-FDA. CMB was ionized by positive electrospray ionization (ESI) as the ionization source and analysed using multiple reaction monitoring (MRM) as the mass analyser mode. CMB and pemigatinib (PMT) were resolved on the C18 column, with an isocratic mobile phase. The CMB calibration curve showed linearity in the concentration range of 1–3000 ng/mL. The intra- and inter-day accuracy and precision were −7.67–4.48% and 0.46–6.99%, respectively. The lower limit of quantification (LLOQ) of 0.94 ng/mL confirmed the sensitivity of the UPLC-MS/MS analytical method. The intrinsic clearance (Clint) and in vitro half-life (t1/2) of CMB were 61.85 mL/min/kg and 13.11 min, respectively. CMB showed a high extraction ratio. The present study is the first to develop, establish, and standardize UPLC-MS/MS for the purpose of quantifying and evaluating the metabolic stability of CMB.

Capmatinib (CMT) has been recently approved for the treatment of non-small cell lung cancer by the United States Food and Drug Administration (USFDA). Till date, the degradation mechanism of CMT in different stress conditions is not known. Moreover, degradation products (DPs) of the drug are yet to be identified. Characterization study on degradation products of CMT has not been reported before. Furthermore, no previously reported literature is available on the stability-indicating method of CMT. Owing to the lack of such scientific reports, we developed a sensitive, stability-indicating method for CMT which can resolve it from all its degradation products. The method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH Q2 [R1]) guideline. We studied and established the degradation mechanism of CMT in different stress conditions. One degradation product (DP2) was isolated and characterized using 1 H NMR. The degradation products (DP1, DP2 and DP3) of the drug have been identified and characterized for the first time by using high-resolution mass spectrometry and 1 H NMR spectroscopy. CMT was found to become degraded under acidic, basic and photolytic stress conditions in the solution phase to yield three major DPs. The drug was found to be stable in neutral hydrolysis, oxidation and thermal stress conditions. DP1 was formed under acidic and basic hydrolytic conditions, whereas DP2 and DP3 were formed under photolytic conditions. Characterization of all the DPs has been carried out to establish their structures and understand the molecular mechanism behind the degradation of the drug. Few studies reported quantitative analysis of CMT and its metabolites in biological fluids. However, this is the first study to identify the unknown DPs of CMT and the mechanism of its degradation. Moreover, this article reports a stability-indicating analytical method for CMT which has not yet been reported in any literature.

Tailoring the photoluminescence of capmatinib towards a novel ultrasensitive spectrofluorimetric and HPLC-DAD monitoring in human serum; investigation of the greenness characteristics

Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study

Capmatinib improves insulin sensitivity and inflammation in palmitate-treated C2C12 myocytes through the PPARδ/p38-dependent pathway

Capmatinib attenuates lipogenesis in 3T3-L1 adipocytes through an adenosine monophosphate-activated protein kinase-dependent pathway