Development and Validation of a Rapid and Sensitive Method for the Simultaneous Estimation of Gemigliptin and Teneligliptin in Bulk and Dosage Forms by Using Liquid Chromatography-tandem Mass Spectrometry

Author(s): Amrish Chandra*, Ramji Rathod, Faraat Ali, Anuj Prakash, Robin Kumar, Gyanendra Nath Singh

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 8 , 2020


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Graphical Abstract:


Abstract:

Background: A simple and sensitive ultra-performance liquid chromatography-mass spectrometry method was developed and validated to measure the concentrations of gemigliptin (GEM) and teneligliptin (TEN) using pioglitazone (PIO) as an internal standard.

Methods: Chromatographic separation of two gliptins was achieved on a C-18 (100 mm X 2.1 mm, 2.7 μm) column using a mobile phase consisting of formic acid in water (0.1 % v/ v): acetonitrile in gradient elution. Electrospray ionization (ESI) source was operated in positive mode (ionization). Targeted MS-MS mode on a quadrupole time of flight (Q-TOF) mass spectrometer was used to quantify the drugs utilizing the mass transitions of 490.1 (m/z), 427.2 (m/z) and 357.1 (m/z) for GEM, TEN 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 between the concentration ranges of 509.8-1529.4 ng mL-1 and 510.6-1531.7 ng mL-1 for GEM and TEN, respectively. Precision and accuracy results were found to be within the acceptable limits. The mean recovery was found to be 98.8± 0.76 % (GEM) and 98.6 ±0.98 % (TEN), respectively.

Conclusion: The optimized validated UPLC-QTOF (MS-MS) method offered the advantage of shorter analytical times and higher sensitivity and selectivity to the nanogram level.

Keywords: UPLC-QTOF-MS, liquid chromatography, gemigliptin, teneligliptin, DPP-4 inhibitor, drugs.

[1]
Kim, S.H.; Yoo, J.H.; Lee, W.J.; Park, C.Y. Gemigliptin: An update of its clinical use in the management of type 2 diabetes mellitus. Diabetes Metab. J., 2016, 40(5), 339-353.
[http://dx.doi.org/10.4093/dmj.2016.40.5.339] [PMID: 27766241]
[2]
Kim, S.H.; Lee, S.H.; Yim, H.J. Gemigliptin, a novel dipeptidyl peptidase 4 inhibitor: first new anti-diabetic drug in the history of Korean pharmaceutical industry. Arch. Pharm. Res., 2013, 36(10), 1185-1188.
[http://dx.doi.org/10.1007/s12272-013-0171-x] [PMID: 23771499]
[3]
M., K. Teneligliptin: A DPP-4 inhibitor for the treatment of Type 2 Diabetes. Diabetes Metab. Syndr. Obes., 2013, 6, 187.
[http://dx.doi.org/10.2147/DMSO.S35682]
[4]
Bronson, J.; Black, A.; Dhar, T.G.M.; Ellsworth, B.A.; Merritt, J.R. Chapter Twenty-Eight - To Market, To Market. Ann. Reports Med. Chemi., 2013, 471-546.
[http://dx.doi.org/10.1016/B978-0-12-417150-3.00028-4]
[5]
Kurbanoglu, S.; Miguel, P.R.S.; Uslu, B.; Ozkan, S.A. Stability-indicating UPLC method for the determination of Bisoprolol Fumarate and Hydrochlorothiazide: Application to dosage forms and biological sample. Chromatographia, 2014, 77, 365-371.
[http://dx.doi.org/10.1007/s10337-013-2606-4]
[6]
Otasevic, B. M. S. Z. G. J. P. A. UPLC method for determination of Moxonidine and its degradation products in active pharmaceutical ingredient and pharmaceutical dosage form. Chromatographia, 2014, 77(1), 109-118.
[http://dx.doi.org/10.1007/s10337-013-2580-x]
[7]
Park, S.I.; Lee, H.; Oh, J.; Lim, K.S.; Jang, I.J.; Kim, J.A.; Jung, J.H.; Yu, K.S. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects. Drug Des. Devel. Ther., 2015, 9, 729-736.
[http://dx.doi.org/10.2147/DDDT.S75980] [PMID: 25678778]
[8]
Chitlange, S. R. D. G. S. Estimation of Anti Diabetic Teneligliptin in Bulk and Formulation by Densitometric and Spectrophotometric Method. Anal. Chem. Lett., 2017, 7(4), 556-566.
[http://dx.doi.org/10.1080/22297928.2017.1364664]
[9]
Sen, A. H. D. S. D. Z. A. M. R. C. V. Analytical method development and validation for simultaneous estimation of Teneligliptin hydrobromide hydrate and Metformin hydrochloride from its pharmaceutical dosage form by three different UV spectrophotometric methods. J. Appl. Pharm. Sci., 2016, 157-165.
[http://dx.doi.org/10.7324/JAPS.2016.60924]
[10]
Kumar, T. V. S. N. N. S. Y. L. M. Method development, validation, and stability studies of Teneligliptin by RP-HPLC and identification of degradation products by UPLC Tandem Mass Spectroscopy. J. Anal. Sci. Technol., 2016, 7(1)
[http://dx.doi.org/10.1186/s40543-016-0107-4]
[11]
Shantikumar, S.; Satheeshkumar, N.; Srinivas, R. Pharmacokinetic and protein binding profile of peptidomimetic DPP-4 inhibitor - Teneligliptin in rats using liquid chromatography-tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2015, 1002, 194-200.
[http://dx.doi.org/10.1016/j.jchromb.2015.08.023] [PMID: 26340762]
[12]
Ali, F.; Nandi, U.; Trivedi, M. Quantitative characterization and pharmaceutical compatibility between teneligliptin and widely used excipients by using thermal and liquid chromatography tandem mass spectrometry techniques. J. Therm. Anal. Calorim., 2018, 132, 385.
[http://dx.doi.org/10.1007/s10973-018-6962-z]


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Article Details

VOLUME: 16
ISSUE: 8
Year: 2020
Published on: 27 September, 2020
Page: [1104 - 1111]
Pages: 8
DOI: 10.2174/1573412915666190523112754
Price: $65

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