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

Development and validation of a rapid and sensitive UPLC–MS/MS assay for the quantification of tofacitinib in human plasma

“…Acetonitrile with ammonium acetate buffer gave better sensitivity and sharper peaks for TOF and TOF‐13C3 15 N than methanol. It was observed that equal proportions of aqueous and organic media in the mobile phase resulted in early elution of TOF as observed previously (Abdelhameed et al, ; Kadi et al, ) on Gemini C 18 and Cosmosil C 18 columns with considerable matrix interference. Further, when the aqueous phase was kept at ≥60%, there was excessive retention of TOF leading to an analysis time of ~10 min.…”

“…However, the recovery obtained was <70% and selectivity was significantly affected with considerable matrix interference owing to repeated clogging of the column. Kadi et al () and Abdelhameed et al () reported a mean recovery of ≥98% for TOF from 1000 μL of plasma by LLE with diethyl ether in the presence of glycine buffer. Thus, LLE was tested with different solvents like diethyl ether, ethyl acetate, n ‐hexane, dichloromethane and MTBE.…”

“…For the extraction of TOF from various biological matrices all three conventional procedures were employed namely, protein precipitation (PPT) (Paniagua et al, ), liquid–liquid extraction (LLE) (Abdelhameed et al, ; Kadi et al, ; Kumar et al, ) and solid‐phase extraction (Dowty et al, ; Krishnaswami, Wang, et al, ; Krishnaswami, Boy, et al, ; Menon et al, ; Sharma et al, ). Initially, PPT was tried with acetonitrile and methanol in the presence of a base.…”

“…To obtain better selectivity and sensitivity as well as shorter analysis time, appropriate selection of chromatographic conditions like mobile phase and its pH, column and flow rate was essential. In the majority of the methods (Abdelhameed et al, ; Dowty et al, ; Kadi et al, ; Kumar et al, ; Paniagua et al, ; Sharma et al, ) the analysis time was ≥4 min. Initially, some reversed‐phase columns like Gemini C 18 (150 × 4.6 mm, 5.0 μm), Cosmosil C 18 (100 × 4.6 mm, 5.0 μm) and Symmetry C 18 (100 × 4.6 mm, 5.0 μm) were tested using formic acid–ammonium formate, acetic acid–ammonium acetate buffer and methanol–acetonitrile in different ratios.…”

“…Several bioanalytical methods are reported to determine TOF as a single analyte (Dowty et al, 2014;Krishnaswami, Wang, et al, 2015;Krishnaswami, Boy, et al, 2015;Kumar et al, 2015;Menon et al, 2016;Paniagua et al, 2005), in combination with other kinase inhibitors (Abdelhameed, Attwa, & Kadi, 2017;Kadi, Abdelhameed, Darwish, Attwa, & Bakheit, 2016) or with methotrexate, an antirheumatic drug . TOF has been determined in different biological samples such as human plasma (Abdelhameed et al, 2017;Dowty et al, 2014;Kadi et al, 2016;Krishnaswami, Boy, et al, 2015;Menon et al, 2016), human serum (Krishnaswami, Wang, et al, 2015), human urine (Abdelhameed et al, 2017;Krishnaswami, Wang, et al, 2015), nonhuman primate blood (Paniagua et al, 2005) and rat plasma (Kumar et al, 2015;Sharma et al, 2015). Mainly liquid chromatography with a mass spectrometry detector has been used for determination of TOF in these matrices except for one method with UV detection (Kumar et al, 2015).…”