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 water, 0.1%v/v: acetonitrile in gradient elution. Electrospray ionization (ESI) source was operated in the 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.
Conclusion: 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.
Keywords: UPLCQ-TOF-MS, alogliptin, linagliptin, saxagliptin, sitagliptin, metformin.
Graphical Abstract
[1]
Seino, Y.; Yabe, D. ALOgliptin benzoate for the treatment of type 2 diabetes. Expert Opin. Pharmacother., 2014, 15(6), 851-863.
[http://dx.doi.org/10.1517/14656566.2014.898750] [PMID: 24646052]
[http://dx.doi.org/10.1517/14656566.2014.898750] [PMID: 24646052]
[2]
Deacon, C.F.; Holst, J.J. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin. Investig. Drugs, 2010, 19(1), 133-140.
[http://dx.doi.org/10.1517/13543780903463862] [PMID: 19947894]
[http://dx.doi.org/10.1517/13543780903463862] [PMID: 19947894]
[3]
Agrawal, R.; Jain, P.; Dikshit, S.N. Linagliptin: a novel methylxanthin based approved dipeptidyl peptidase-4 inhibitor. Curr. Drug Targets, 2012, 13(7), 970-983.
[http://dx.doi.org/10.2174/138945012800675731] [PMID: 22420306]
[http://dx.doi.org/10.2174/138945012800675731] [PMID: 22420306]
[5]
Kania, D.S.; Gonzalvo, J.D.; Weber, Z.A. Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. Clin. Ther., 2011, 33(8), 1005-1022.
[http://dx.doi.org/10.1016/j.clinthera.2011.06.016] [PMID: 21802144]
[http://dx.doi.org/10.1016/j.clinthera.2011.06.016] [PMID: 21802144]
[6]
United States Prescribing Information for Januvia® (Sitagliptin phosphate) Merck and Co., Inc 2006.
[7]
Plosker, G.L. Sitagliptin: a review of its use in patients with type 2 diabetes mellitus. Drugs, 2014, 74(2), 223-242.
[http://dx.doi.org/10.1007/s40265-013-0169-1] [PMID: 24407560]
[http://dx.doi.org/10.1007/s40265-013-0169-1] [PMID: 24407560]
[8]
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, 7, 365-371.
[http://dx.doi.org/10.1007/s10337-013-2606-4]
[http://dx.doi.org/10.1007/s10337-013-2606-4]
[9]
Otasevic, B.; Milovanovic, S.; Zecevic, M.; Golubovic, J.; Protic, 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]
[http://dx.doi.org/10.1007/s10337-013-2580-x]
[10]
Supriya, P. Madhavi Latha, N development and validation of uv spectrophotometric and reversed-phase high-performance liquid chromatography pda methods for the estimation of ALOgliptin benzoate. Asian J Pharm Clin Res, 2016, 9(1), 282-287.
[11]
Kun, Z.; Panqin, M.; Wenna, J.; Xiangrong, Z. A developed HPLC method for the determination of ALOgliptin Benzoate and its potential impurities in bulk drug and tablets. Asian. J. Pharm. Sci., 2015, 10(2), 152-158.
[12]
Zhou, Y.; Zhou, W.; Sun, L.; Zou, Q.; Wei, P.; OuYang, P. Characterization of process-related impurities including forced degradation products of ALOgliptin benzoate and the development of the corresponding reversed-phase high-performance liquid chromatography method. J. Sep. Sci., 2014, 37(11), 1248-1255.
[http://dx.doi.org/10.1002/jssc.201301384] [PMID: 24616424]
[http://dx.doi.org/10.1002/jssc.201301384] [PMID: 24616424]
[13]
Abdel-Ghany, M.F.; Ayad, M.F.; Tadros, M.M. Enhanced LC-MS/MS analysis of ALOgliptin and pioglitazone in human plasma: Applied to a preliminary pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1058, 93-101.
[http://dx.doi.org/10.1016/j.jchromb.2017.04.043] [PMID: 28528664]
[http://dx.doi.org/10.1016/j.jchromb.2017.04.043] [PMID: 28528664]
[14]
Shereen, M.; Ehab, F.E.; Mohamed, M.E.; Bassam, M.A. Enhanced LC-MS/MS determination of ALOgliptin and Metformin in plasma: Application to a pharmacokinetic study. Microchem. J., 2017, 130, 360-365.
[http://dx.doi.org/10.1016/j.microc.2016.10.002]
[http://dx.doi.org/10.1016/j.microc.2016.10.002]
[15]
Hemavathi, G.; Hipparagi, S.M. Sensitive LC-MS/MS Method for the Simultaneous Determination of ALOgliptin and Voglibose in Human Plasma. J. Anal. Bioanal. Tech., 2017, 8, 354.
[16]
El-Bagary, R.; Elkady, E.; Ayoub, B. Spectrofluorometric determination of Linagliptin in bulk and in the pharmaceutical dosage form. Eur. J. Chem., 2014, 5(2), 380-382.
[http://dx.doi.org/10.5155/eurjchem.5.2.380-382.845]
[http://dx.doi.org/10.5155/eurjchem.5.2.380-382.845]
[17]
Vemula, P.; Dodda, D.; Balekari, U.; Panga, S.; Veeresham, C. Simultaneous determination of linagliptin and metformin by reverse phase-high performance liquid chromatography method: An application in quantitative analysis of pharmaceutical dosage forMS. J. Adv. Pharm. Technol. Res., 2015, 6(1), 25-28.
[http://dx.doi.org/10.4103/2231-4040.150368] [PMID: 25709966]
[http://dx.doi.org/10.4103/2231-4040.150368] [PMID: 25709966]
[18]
El-Bagary, R.I.; Elkady, E.F.; Ayoub, B.M. Liquid chromatographic determination of linagliptin in bulk, in plasma and in its pharmaceutical preparation. Int. J. Biomed. Sci., 2012, 8(3), 209-214.
[PMID: 23675275]
[PMID: 23675275]
[19]
Prasad, P.B.N.; Satyanaryana, K.; Krishnamohan, G. Development and Validation of A Stability Indicating Method for Simultaneous Determination of Metformin Hydrochloride and Linagliptin in A Formulation by RP-HPLC. International Journal of Pharma Research & Review, 2016, 5(6), 16-22.
[20]
Mahesh, A.; Sree Harsha, N.; Bandar, E.A.; Anroop, N.; Venugopala, K.N. simultaneous determination of metformin and three gliptins in pharmaceutical formulations using rp hplc: application to stability studies on linagliptin tablet formulation. Indian Journal of Pharmaceutical Education and Research, 2014, 48(4), 45-53.
[http://dx.doi.org/10.5530/ijper.48.4.7]
[http://dx.doi.org/10.5530/ijper.48.4.7]
[21]
Nagaraj Kumar, N.; Sunil, S.J.; Rajendraprasad, M.; Sunil Kumar, S. An ultra-high performance liquid chromatography-tandem mass spectrometry method for the quantification of Linagliptin in human plasma. RSC Advances, 2016, 6, 66756-66766.
[http://dx.doi.org/10.1039/C6RA10450A]
[http://dx.doi.org/10.1039/C6RA10450A]
[22]
Mahamad Shafi, S.S.; Arifa, B.; Saradhi, N.D.V.R. Bioanalytical Method Development and Validation of Linagliptin in Plasma Through LCMS/MS. Int. J. Bioassays, 2014, 3(07), 3146-3151.
[23]
Mohammed Al, B.; Hassan, A.A.; Sadique, A.J.; Keddal, G.L.; Mufarreh, A.; Jessica, W.; Sami El, D. Development and Validation of LC-MS/MS Method for simultaneous determination of metformin and four gliptins in human plasma. Chromatographia, 2017, 80(6), 891-899.
[http://dx.doi.org/10.1007/s10337-017-3288-0]
[http://dx.doi.org/10.1007/s10337-017-3288-0]
[24]
Shantikumar, S.; Satheeshkumar, N.; Prasanth, B.; Lingesh, A.; Paul, D.; Srinivas, R. A sensitive and selective Liquid Chromatography-Mass Spectrometry method for simultaneous estimation of anti-diabetic drugs inhibiting the DPP-4 enzyme in human plasma: overcoming challenges associated with low recovery and sensitivity. Anal. Methods, 2015, 7(15), 6198-6206.
[http://dx.doi.org/10.1039/C5AY00342C]
[http://dx.doi.org/10.1039/C5AY00342C]
[25]
Prasad, P.; Satyanaryana, K.; Krishnamohan, G. development and validation of a method for simultaneous determination of Metformin and Saxagliptin in a Formulation by RP-HPLC. Am. J. Anal. Chem., 2015, 6, 841-850.
[http://dx.doi.org/10.4236/ajac.2015.611080]
[http://dx.doi.org/10.4236/ajac.2015.611080]
[26]
Xiaohui (Sophia), Xu; Roger, D; Huidong, G; Lisa, J. C; Hong, S; Laura, C; David, W.B.; Mark, K; Bruce, S; William, G.H; Mark, E.A Liquid chromatography and tandem mass spectro metrymethod for the quantitative determination of Saxagliptin and its major pharmacologically active 5-monohydroxy metabolite in human plasma: Method validation and overcoming specific and nonspecific binding at low concentrations. Jour. of Chromat. B, 2012.889– 890, 77-86.
[27]
Shailaja, B.J.; Swati, K.K.; Deepali, L.D.; Amol, M.J.; Praveen, D.C. development and validation of rp-hplc and hptlc methods for simultaneous estimation of sitagliptin phosphate and metformin hydrochloride in bulk and dosage form. Ind J Pharm Edu Res, 2013, 47(1), 13-16.
[28]
Anil, D.; Rizwanbasha, K.; Jaya, S.K.; Venkat, M.; Malay, K.S. bioanalytical method development and validation of sitagliptin phosphate by rp-hplc and its application to pharmacokinetic study. Int. J. Pharm. Pharm. Sci., 2012, 4(2), 691-694.
[29]
Nirogi, R.; Kandikere, V.; Mudigonda, K.; Komarneni, P.; Aleti, R.; Boggavarapu, R. Sensitive liquid chromatography tandem mass spectrometry method for the quantification of sitagliptin, a DPP-4 inhibitor, in human plasma using liquid-liquid extraction. Biomed. Chromatogr., 2008, 22(2), 214-222.
[http://dx.doi.org/10.1002/bmc.926] [PMID: 17939170]
[http://dx.doi.org/10.1002/bmc.926] [PMID: 17939170]
[30]
Ayoub, B. UPLC simultaneous determination of Empagliflozin, Linagliptin, and Metformin. RSC Advances, 2015, 5(116), 95703-95709.
[http://dx.doi.org/10.1039/C5RA17231D]
[http://dx.doi.org/10.1039/C5RA17231D]
Article Metrics
10