The Effect of Posaconazole and Isavuconazole on the Pharmacokinetics of Erdafitinib in Beagle Dogs by UPLC-MS/MS

Abstract

Objective: A robust, quick, and reliable ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for the quantification of erdafitinib in beagle dog plasma was developed and validated to evaluate the changes of posaconazole and isavuconazole on the pharmacokinetics of erdafitinib in beagle dogs, respectively.Methods: This experiment adopted a three-period self-control experimental design. In the first period (group A), erdafitinib was orally administered to six beagle dogs at a dose of 4 mg/kg. In the second period (group B), the same six beagle dogs were orally given posaconazole at a dose of 7 mg/kg, and after 30 min, erdafitinib was orally given. In the third period (group C), isavuconazole at a dose of 7 mg/kg was given orally, and then, erdafitinib was orally given. At the different time points after erdafitinib was given in the three periods, the blood samples were collected. The concentration of erdafitinib was detected by the developed UPLC-MS/MS method. DAS 2.0 was used to calculate the pharmacokinetic parameters of erdafitinib.Results: Erdafitinib had a good linear relationship in the range of 1–500 ng/ml, and the lower limit of quantification was 1 ng/ml. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. After erdafitinib was combined with posaconazole, the Cmax and AUC0→t of erdafitinib increased by 27.19% and 47.62%, respectively, and the t1/2 was prolonged to 6.33 h. After erdafitinib was combined with isavuconazole, the Cmax and AUC0→t of erdafitinib increased by 23.13% and 54.46%, respectively, and the t1/2 was prolonged to 6.31 h.Conclusion: A robust and reliable UPLC-MS/MS method was fully optimized and developed to detect the plasma concentration of erdafitinib in beagle dogs. Posaconazole and isaconazole could inhibit the metabolism of erdafitinib in beagle dogs and increase the plasma exposure of erdafitinib.

Effect of Chaihu Shugan Pills on the Pharmacokinetics of Duloxetine and its Metabolite 4-Hydroxyduloxetine in Beagle Dogs: A Herb-Drug Interaction Study

“…e main methods used to detect duloxetine hydrochloride were HPLC [13] and LC-MS [14][15][16]. UPLC-MS/MS technology was a common method for drug-drug interactions (DDIs) and herb-drug interactions (HDIs) [17][18][19](Ruan et al; Xia et al, 2021;Zhu et al, 2019). So, in this study, we optimized the methodology according to the concept and principles of Green Analytical Chemistry (GAC) [20] and established a UPLC-MS/MS for the simultaneous determination of duloxetine as well as its metabolite 4-hydroxyduloxetine in beagle dog plasma.…”

Advancing posaconazole quantification analysis with a new reverse-phase HPLC method in its bulk and marketed dosage form

“…After the initial method development trials were conducted, an optimized trial was carried forward for analytical method validation according to ICH guidelines. [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94] Validation of the optimized HPLC method The validation of an analytical method is critical for ensuring that the method is appropriate and reliable for its intended usage. In this study, the optimized analytical technique was subjected to a series of validation experiments recommended by the International Conference on Harmonization (ICH) Q2(R1) guidelines in order to evaluate its performance under various situations.…”

Advancing posaconazole quantification analysis with a new reverse-phase HPLC method in its bulk and marketed dosage form

“…After the initial method development trials were conducted, an optimized trial was carried forward for analytical method validation according to ICH guidelines. [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94] Validation of the optimized HPLC method The validation of an analytical method is critical for ensuring that the method is appropriate and reliable for its intended usage. In this study, the optimized analytical technique was subjected to a series of validation experiments recommended by the International Conference on Harmonization (ICH) Q2(R1) guidelines in order to evaluate its performance under various situations.…”