Simultaneous Determination of Alogliptin, Linagliptin, Saxagliptin, and Sitagliptin in Bulk Drug and Formulation by UPLC Q-TOF-MS

Abstract

Background: A simple and sensitive Ultra Performance Liquid Chromatography-Mass Spectrometry method was developed and validated to measure the concentrations of Alogliptin (ALO), Linagliptin (LIN), Saxagliptin (SAX), and Sitagliptin (SIT) using Pioglitazone (PIO) as an internal standard. Methods: Chromatographic separation of six gliptins was achieved on a C-18 column (100×2.1 mm, 2.7 µm) using a mobile phase consisting of Formic acid in the water, 0.1%v/v: Acetonitrile in gradient elution. Electrospray ionization (ESI) source was operated in positive ion mode. Targeted MS/MS mode on a QTOF MS was used to quantify the drug utilizing the transitions of 340.1(m/z), 473.2 (m/z), 316.2 (m/z), 408.1 (m/z), and 357.1 (m/z) for ALO, LIN, SAX, SIT and PIO respectively. Results: As per ICH Q2R1 guidelines, a detailed validation of the method was carried out and the standard curves were found to be linear over the concentration ranges of 1516.0-4548.1 ng mL-1, 519.8-1559.4 ng mL-1, 1531.4-4594.3 ng mL-1and 1519.6-4558.8 ng mL-1 for ALO, LIN, SAX and SIT respectively. Precision and accuracy results were within the acceptable limits. The mean recovery was found to be 98.8 _ 0.76 % (GEM), 102.2 _ 1.59 % (LIN), 95.3 _ 2.74 % (SAX) and 99.2 _ 1.75 % (SIT) respectively Conclusions: The optimized validated UPLC QTOF-MS/MS method offered the advantage of shorter analytical times and higher sensitivity and selectivity. The optimized method is suitable for application in quantitative analysis of pharmaceutical dosage forms for QC laboratory.

Application of experimental design in HPLC method optimization and robustness for the simultaneous determination of canagliflozin, empagliflozin, linagliptin, and metformin in tablet

“…Few other analytical methods were described for the simultaneous determination of LIG in combination with other antidiabetic agents using HPTLC (El-Kimary et al, 2016;Patel et al, 2020), UPLC/ UV (Ayoub, 2015;Vankalapati et al, 2021), and LC-MS/MS (Al Bratty et al, 2017;Rathod et al, 2020) methods, either in their pharmaceutical dosage form or in human plasma. In addition, other methods were reported for the determination of EMG either alone (Abdel-Ghany et al, 2018;Ayoub, Emam, et al, 2017;Manoel et al, 2021) or in combination with MEF Munde et al, 2020;Riaz et al, 2020).…”

Multivariate optimization of liquid chromatographic conditions for determination of dapagliflozin and saxagliptin, application to an in vitro dissolution and stability studies

“…Literature survey revealed that there were few reports published on the simultaneous quantification of dapagliflozin and saxagliptin using UV [8], HPTLC [9], HPLC [10][11][12][13][14][15][16][17][18], and LC-MS [19,20] techniques in bulk drug and pharmaceutical dosage forms. Few methods were reported for analysis of dapagliflozin and saxagliptin separately [21][22][23][24] and in combination with other drugs [25][26][27][28][29]. Literature methods concerted largely on the development and validation of a RP-HPLC methods using different organic phases at different wavelengths and sensitive spectroscopic methods.…”