## 1 Introduction  
Urothelial carcinoma or transitional cell carcinoma is the most common type of cancer, affecting the transitional cells of the urinary system. It accounts for the majority of bladder cancer diagnosis with more than 90% of bladder cancer cases. It is more common in males than females [1; 2; 3] and one out of five advanced urothelial carcinoma patients has a mutation in the fibroblast growth factor receptor (FGFR) gene, which is responsible for increased tumor cell growth and survival and accompanied with lower sensitivity to immune interventions [4]. Erdafitinib (ERDA) is a potent selective FGFR tyrosine kinase inhibitor [5]. It has been recently approved by the FDA for the treatment of advanced cancer of the urinary bladder [6]. ERDA binds to and blocks the enzymatic activity of cell proteins, FGFRs [7]. It also binds to other proteins, including tyrosine kinase 4 (FLT4), vascular endothelial growth factor receptor 2 (VEGF2) and platelet-derived growth factor receptor alpha (PDGFRA) [3]. It is currently being evaluated as monotherapy or combination therapy with anti-programmed cell death protein-(PD-1) in a mouse model with PD-1 blocked in an autochthonous lung cancer; erdafitinib monotherapy was effective but without survival benefit and anti-PD-1 treatment alone was ineffective. However, erdafitinib and an anti-PD-1 combination induced significant tumor regression and improved survival rate [8].  
It was reported that ERDA was well tolerated in Japanese patients with advanced or refractory solid tumors [9; 10]. It was absorbed rapidly following single-dose administration with the maximum concentration achieved after 2-3 h and 2-6 h, following multiple daily dosing and the steady state was reached after 8 days of treatment [9]. ERDA pharmacokinetics can be affected by co-administration with other cytochrome P450 inhibitors/inducers, such as some antifungal drugs. The co-administration of ERDA with funconazole, posaconazole and isavuconazole (CYP3A4 inhibitor) or itraconazole (CYP2C9 inhibitor) increases ERDA blood levels [11; 12]. Race, age and mild hepatic impairment have no significant effect on ERDA blood concentration (11).  
The toxicity profile of ERDA has shown ocular toxicity even after a short treatment duration [13; 14; 15]. ERDA has some adverse effects, including cases of elevated aspartate transaminase (AST), alanine aminotransferase (ALT) and alkaline phosphatase [16; 17]. ERDA most common adverse effects are dysgeusia, stomatitis, diarrhea, hyperphosphatemia and dry mouth [7]. Moreover, hyperphosphatemia was a common side effect in patients treated with ERDA [15].  
There is a large inter-individual difference in ERDA pharmacokinetics, leading to variability in doses required to achieve target concentration [9]. To achieve this balance and to individualize drug dosing, therapeutic drug monitoring (TDM) of ERDA is required. ERDA dose is considered based on the presence of susceptible FGFR genetic alteration in patient tumor. However, the source of variability is multifactorial, including pathophysiology, environment, diet, drug-drug interaction. All these factors have an impact on ERDA pharmacokinetics and pharmacodynamics. In order to achieve this goal, it is necessary to develop bio-analytical assays that are reliable, very sensitive and fast. Few methods were published using HPLC-UV, but they are characterized by high limits of quantitation (50 ng/mL) [18] with others using LC-MS/MS [19; 20]. The present work was formulated to develop a novel, simple, sensitive, accurate and validated method for the determination and quantification of ERDA in human plasma that could be applied to the TDM, toxicokinetic and pharmacokinetic studies.