Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC–MS/MS

Liquid chromatographic-tandem mass spectrometric assay for simultaneous quantitation of tofacitinib, cabozantinib and afatinib in human plasma and urine

“…Moreover, one recent study reported AFB simultaneous determination with other TKIs namely, vandetanib, pazopanib, and dasatinib in human plasma using HPLC-DAD [14] with the AFB linearity range 0.7 -7.0 µgmL -1 , which is higher than its reported C max (maximum plasma concentration) value of 6.19 -7.58 ngmL -1 [11] and 11.6 -40.8 ngmL -1 after administration of single and multiple doses of different AFB concentrations [15]. On the other hand, individual CBZ quantification was reported using HPLC-UV [16], LC-MS/MS [17,18] in rat plasma with one study using micellar enhanced spectrofluorimetry in human plamsa [19].…”

Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

“…This is often done by rotor-stator [59][60][61], micro-pellet homogenizer [62,63], or acoustic cell disruption [64] with addition of water [59], saline [65], drug-free plasma [61], or a BSAsolution [66]. Quantitative analysis of TKIs in tissue is mainly done to evaluate target site drug-exposure in patients or for transporter elucidation in small animals.…”

“…A difficulty in tissue-level analysis is the solubility of drugs in the homogenized matrix. For this reason, drug-free plasma [61], or a BSA-solution [66] is added for improved solubility due to protein binding [66], or direct protein precipitation with organic solvents like methanol and/or acetonitrile is performed [60,64]. An issue that may rise is the drug-stability in tissue samples, especially tissues involved in drug metabolism, like liver samples.…”

“…axitinib Inlyta AG013736 Renal cell carcinoma VEGFR1-3, c-KIT, PDGFR No [15,101,127] bosutinib Bosulif SKI-606 Ph+CML (Bcr-Abl) BCR-ABL, Src, Lyn, Hck No [127] cabozantinib Cabometyx, Cometriq XL184 Medullary thyroid cancer c-Met, VEGFR2 No [64,147] ceritinib Zykadia LDK378 ALK+ NSCLC ALK No [22,117] crizotinib Xalkori PF02341066 ALK-fusion NSCLC ALK, ROS1, c-Met No [32,92,133] dabrafenib Tafinlar GSK2118436 B-raf V600E mut. melanoma B-Raf-V600E No [148] dasatinib Sprycel BMS354825 Ph+CML (Bcr-Abl) BCR-ABL, PDGFR, Src, c-Kit, … No [7,15,23,31,47,62,83,95,99,114,119,124,126,130,149] erlotinib Tarceva OSI774 NSCLC EGFR, JAK2V617F No [15,23,51,61,67,84,91,105,107,114,118,124,125,128,129,135,1 50,151] gefitinib Iressa ZD1839 NSCLC EGFR No [15,52,53,107,114,124,125,152] ibrutinib Imbruvica PCI32765 MCL, CLL, WM Brutons TK (BTK) Yes, Cys481 [72,76,98,113,145] imatinib Gleevec, Glivec ST1571 Ph+CML (Bcr-Abl), GIST BCR-ABL, PDGFR, SCF, c-KIT No [7,…”

A sensitive LC–MS/MS method for simultaneous determination of cabozantinib and its metabolite cabozantinib N‐oxide in rat plasma and its application in a pharmacokinetic study

“…Our group developed a stability‐indicating LC method and identified its major degradation products by LC‐TOF‐MS and LC–MS/MS (Wu et al, ). LC–MS/MS (Abdelhameed, Attwa, & Kadi, ; Su et al, ) and UPLC–MS/MS (Wang et al, ) methods have been reported to determine CBZ in rat plasma or tissues. However, these reported methods emphasized the determination of CBZ only, and did not pay any attention to its metabolites.…”