Back
 AJAC  Vol.3 No.12 , December 2012
Rapid LC-ESI-MS-MS Method for the Simultaneous Determination of Sitagliptin and Pioglitazone in Rat Plasma and Its Application to Pharmacokinetic Study
Abstract: A liquid chromatography tandem mass spectrometry (LC-MS/MS) based method was developed for the simultaneous monitoring plasma levels of Sitagliptin (STG) and Pioglitazone (PIO) for applicability to pharmacokinetic studies. The method was based on HPLC separation on the reversed phase Phenomenex Synergy C18 column (30 mm length, 4.6 mm internal diameter, and 4.0 μm particle size) at a temperature of 40?C using a binary gradient mobile phase consisting of methanol and 2 mM ammonium acetate buffer pH adjusted to 4.5 with acetic acid, at a flow rate of 1 mL?min?1. Tolbutamide was used as an internal standard. Detection of analytes was achieved with LC-MS/MS system in Multiple Reaction Monitoring (MRM) mode. The method was validated over concentration range of 10.98 - 2091.77 ng?mL?1 for SIT and 8.25 - 1571.63 ng?mL?1 for PIO and lower limit of quantification was 10.98 ng?mL?1 and 8.25 ng?mL?1 for STG and PIO respectively. Recoveries from spiked controls were within acceptance criteria for all the analytes and internal standard at all QC levels. Within batch and between batch accuracy for STG was found within 96.9% - 100.3% and for PIO was found within 100.0% - 104.3%. Within batch and between batch precision for STG was less than 3.1% CV (coefficient of variation) and for PIO was less than 5.3% CV at all concentrations levels. This method was successfully applied to monitor pharmacokinetics profile of both STG and PIO on simultaneous oral administration to rats. This method can be applicable for pharmacokinetic drug-drug interaction studies.
Cite this paper: S. Gananadhamu, V. Laxmikanth, S. Shantikumar, V. Sridhar, C. Geetha and C. Sandhya, "Rapid LC-ESI-MS-MS Method for the Simultaneous Determination of Sitagliptin and Pioglitazone in Rat Plasma and Its Application to Pharmacokinetic Study," American Journal of Analytical Chemistry, Vol. 3 No. 12, 2012, pp. 849-858. doi: 10.4236/ajac.2012.312112.
References

[1]   A. Bergman and D. Ebel, “Absolute Bioavailability of Sitagliptin, an Oral Dipeptidyl Peptidase-4 Inhibitor in Healthy Volunteers,” Biopharmaceutics & Drug Disposition, Vol. 28, No. 6, 2007, pp. 315-322. doi:10.1002/bdd.560

[2]   G. A. Herman and A. Bergman, “Pharmacokinetics and Pharmacodynamic—Effects of the Oral DPP-4 Inhibitor Sitagliptin in Middle-Aged Obese Subjects,” Journal of Clinical Pharmacology, Vol. 46, No. 8, 2006, pp. 876- 886. doi:10.1177/0091270006289850

[3]   M. L. Christensen, B. Meibohm, E. V. Capparelli, P. Velasquez-Mieyer, G. A. Burghen and W. V. Tamborlane, “Single- and Multiple-Dose Pharmacokinetics of Pioglitazone in Adolescents with Type 2 Diabetes,” Journal of Clinical Pharmacology, Vol. 45, No. 10, 2005, pp. 1137-1144. doi:10.1177/0091270005279578

[4]   Bala, S. and R. Prameela, “Development and Validation of Spectrophotometric Method for the Determination of DPP4 Inhibitor, Sitagliptin in Its Pharmaceutical Dosage Forms,” International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 2, No. 4, 2007, pp. 138-142.

[5]   R. S. Mehta and D. M. Patel, “UV and Visible Spectrophotometric Analysis of Pioglitazone Hydrochloride in Bulk and Tablets,” Indian Journal of Pharmaceutical Sciences, Vol. 67, No. 4, 2005, pp. 487-489.

[6]   A. J. Meeta, S. S. Pandya and G. Vidyasagar, “A Simple and Sensitive HPTLC Method for Estimation of Pioglitazone in Bulk and Tablet Dosage Forms,” Asian Journal of Research in Chemistry, Vol. 2, No. 2, 2009, pp. 207-209.

[7]   W. Zeng, D. G. Musson, A. L. Fisher, L.Chen, M. S.Schwartz, E. J. Woolf, and A. Q. Wang, “Determination of Sitagliptin in Human Urine and Hemodi-alysate Using Turbulent Flow Online Extraction and Tandem Mass Spectrometry,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 46, No. 3, 2008, pp. 534-542.

[8]   T. Rad-hakrishna, R. D. Sreenivas and G. Om Reddy, “Determination of Pioglitazone Hydrochloride in Bulk and Pharmaceutical Formulations by HPLC and MEKC Methods,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 29, No. 4, 2002, pp. 593-607. doi:10.1016/S0731-7085(02)00036-5

[9]   E. I. Ramzia, E. F. Ehab and A. M. Bassam, “Liquid Chromatographic Determina-tion of Sitagliptin Either Alone or in Ternary Mixture with Metformin and Sitagliptin Degradation Product,” Talanta, Vol. 85, No. 1, 2011, pp. 673-680. doi:10.1016/j.talanta.2011.04.051

[10]   M. Shyamala, S. Mohideen, T. Satyanarayana, C. NarasimhaRaju, K. P. Suresh and K. Swetha, “Validated RP-HPLC for Simultaneous Estimation of Sitagliptin Phosphate and Metformin Hydrochloride in Tablet Dosage Form,” American Journal of PharmTech Research, Vol. 2, No. 1, 2011, pp. 93-101.

[11]   K. Dipak and K. Rajendra, “Simultaneous Determination of Pioglitazone, Metformin and Glimepiride in Pharmaceutical Preparations Using HPTLC Method,” Journal of Planar Chromatography, Modern TLC, Vol. 24, No. 4, 2011, pp. 331-334.

[12]   K. Ghazala, S. Dinesh, Y. P. Agrawal, S. Neetu, J. Avnish and A. K. Gupta, “Simulta-neous Estimation of Metformin and Sitagliptin in Tablet Dosage Form,” Asian Journal of Biochemical and Pharmaceutical Research, Vol. 2, No. 2, 2011, pp. 352-358.

[13]   M. Jemal, “High-Throughput Quantitative Bioanalysis by LC/MS/MS,” Biomedical Chromatography, Vol. 14, No. 6, 2000, pp. 422-429. doi:10.1002/1099-0801(200010)14:6<422::AID-BMC25>3.0.CO;2-I

[14]   R. N. Xu, L. Fan, M. J. Rieser and T. A. El-Shourbagy, “Recent Advances in High-Throughput Quantitative Bioanalysis by LC-MS/MS,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 44, No. 2, 2007, pp. 342-355. doi:10.1016/j.jpba.2007.02.006

 
 
Top