A Validated Lc-MS/MS Method for Pharmacokinetic Study of Canagliflozin in Healthy Rabbits

Abstract

Objective: A liquid chromatography-tandem mass spectrophotometric (LC-MS/MS) method was developed for quantification of canagliflozin in rabbit plasma employing Liquid-Liquid extraction technique. Methods:Chromatographic separation was achieved on Inertsil ODS 5 µm C18, 50×4.60 mm with 30:70 v/v of 0.01M ammonium acetate: methanol as an isocratic mobile phase with a flow rate of 0.8 ml/min. The developed LC-MS method was applied to assess Cmax, t1/2, AUC0-t, and AUC0-inf of canagliflozin tablet after oral administration in healthy rabbits. Results:The developed method was linear over working range of 5ng/ml to 600ng/ml with a coefficient of correction (r 2 ) = 0.999. The % recovery of the method was found to be 102.05%. The mean intraday and inter-day precision of the method was found to be 0.77 to 3.72%. The Canagliflozin showed Tmax of 1.58±0.2 and mean Cmax, AUC0→t and AUC0→α for Test formulation is 272±13.24, 2571.20±251and 2777.43±276 respectively. Conclusion:The developed method can be applied for routine analysis for quality control and the established LLOQ is sufficiently low to conduct a pharmacokinetic study with any marketing formulation of Canagliflozin in healthy rabbits.

Quantitative determination of canagliflozin in human plasma samples using a validated HPTLC method and its application to a pharmacokinetic study in rats

“…However, the reported HPLC technique with UV detection was less sensitive than the proposed HPTLC technique (Deepan et al, 2017). The sensitivity of eight LC–MS/MS and two UPLC–MS/MS techniques was also better than proposed HPTLC assay but most of these methods were not better in terms of cost, accuracy and precision (Bhatt & Rajkamal, 2018; Deepan et al, 2019; Dong et al, 2018; Iqbal, Ezzeldin, et al, 2015; Kobuchi et al, 2016; Ramisetti et al, 2019; Saibaba et al, 2018; Shah et al, 2019; Shah & Shrivastav, 2018; Udhayavani et al, 2018). Overall, the proposed HPTLC technique for the estimation of CNZ in plasma has been found more simple, time saving and cost effective with good accuracy and precision compared with reported techniques.…”

“…Some high‐performance liquid chromatography (HPLC) methods have been applied for the analysis of CNZ in rat or human plasma (Deepan, Rao, & Dhanaraju, 2017; Dudhe & Kamble, 2016; Iqbal, Khalil, Alanazi, & Al‐Rashood, 2015; Mabrouk, Soliman, El‐Azigy, & Mansour, 2020). Various LC–mass spectrometry (MS)/MS methods have also been reported for the determination and evaluation of pharmacokinetic profile of CNZ in rat or human or rabbit plasma (Bhatt & Rajkamal, 2018; Deepan, Rao, & Dhanaraju, 2019; Dias et al, 2019; Dong et al, 2018; Iqbal, Ezzeldin, et al, 2015; Kobuchi, Yano, Ito, & Sakaeda, 2016; Ramisetti, Atmakuri, Venkatay, & Adireddy, 2019; Saibaba, Pilli, Bimireddy, & Pandiyan, 2018; Shah et al, 2019; Shah & Shrivastav, 2018; Udhayavani, Sastry, Rajan, Tejaswi, & Rajani, 2018). LC–MS/MS‐based quantitative analysis of drugs in biological fluids is the preferred technique owing to its advantages such as sensitivity, selectivity and speed of analysis (Deepan et al, 2019; Iqbal, Ezzeldin, et al, 2015; Shah et al, 2019).…”

Liquid chromatographic methods for the analysis of canagliflozin: concise overview and greener assessment

“…Besides, similar methods have also been reported by other workers using the same extraction solvent (TBME) but differ in their % recovery and quantication limit. [9][10][11][12] In addition to traditional methods, commercially available SPE cartridges, such as Strata X polymeric sorbent, have been used by some workers [13][14][15] for the extraction of CNG from human plasma. Methanol and water were used as extraction solvents and the mean recovery of CNG was 77-98%.…”

“…Besides, similar methods have also been reported by other workers using the same extraction solvent (TBME) but differ in their % recovery and quantification limit. 9–12…”

DEVELOPMENT AND VALIDATION OF UV SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF DOLUTEGRAVIR BY USING QUALITY BY DESIGN (QbD) APPROACH

“…Research Article methods, the QbD approach involves a full understanding of how the analytical technique attributes and operating conditions affect the analytical performance. Factors to study in analytical quality by design" (AQbD) may include the type of analytical technique chosen, reagents used, and instrumental parameters [5][6][7][8][9]. There are similar advantages of applying QbD principles to analytical methods as to manufacturing processes and product.…”