Arzneimittelforschung 2012; 62(09): 425-432
DOI: 10.1055/s-0032-1316374
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Liquid Chromatography – Tandem Mass Spectrometry for the Simultaneous Quantitation of Glipizide, Cilostazol and its Active Metabolite 3, 4-dehydro-cilostazol in Rat Plasma: Application for a Pharmacokinetic Study

T.R. S. Satheeshmanikandan
1   Incozen Therapeutics Private Limited, Spectrum, Discovery Zone, Turkapplly, Hyderabad, Andhra Pradesh, India
,
V. Sridhar
1   Incozen Therapeutics Private Limited, Spectrum, Discovery Zone, Turkapplly, Hyderabad, Andhra Pradesh, India
,
V.V. S. Kanthikiran
1   Incozen Therapeutics Private Limited, Spectrum, Discovery Zone, Turkapplly, Hyderabad, Andhra Pradesh, India
,
V.V. S. Swaroopkumar
1   Incozen Therapeutics Private Limited, Spectrum, Discovery Zone, Turkapplly, Hyderabad, Andhra Pradesh, India
,
K. Mukkanti
2   Center for Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad, Andhra Pradesh, India
› Author Affiliations
Further Information

Publication History

received 23 April 2012

accepted 15 June 2012

Publication Date:
20 July 2012 (online)

Abstract

A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the simultaneous quantitation of glipizide, cilostazol and 3, 4-dehydro-cilostazol in rat plasma was developed and validated. Glimepride was used as an internal standard (IS). The analytes were extracted by using liquid-liquid extraction procedure and separated on a reverse phase C18 column (50 mm×4.6 mm i. d., 5 µ) using acetonitrile: 2 mM ammonium acetate buffer, pH 3.2 (90:10, v/v) as mobile phase at a flow rate 0.4 mL/min in an isocratic mode. Selective reaction monitoring was performed using the transitions m/z 446.4>321.1, 370.2>288.3, 368.3>286.2, and 491.4>352.2 to quantify glipizide, cilostazol, 3, 4-dehydro-cilostazol and glimepride, respectively. Calibration curves were constructed over the range of 25–2 000 ng/mL for glipizide, cilostazol and 3, 4-dehydro-cilostazol. The lower limit of quantitation was 25 ng/mL for all the analytes. The recoveries from spiked control samples were>76% for all analytes and internal standard. Intra and inter day accuracy and precision of validated method were within the acceptable limits of at all concentration. The quantitation method was successfully applied for simultaneous estimation of glipizide, cilostazol and 3, 4-dehydro-cilostazol in a pharmacokinetic drug-drug interaction study in wistar rats.

 
  • References

  • 1 Wensing G. Glipizide: an oral hypoglycemic drug. Am J Med Sci 1989; 298
  • 2 Malecki M. The role of glipizide in the treatment of non-insulin dependent diabetes. Przegl Lek 1996; 53
  • 3 Ogonowski J. Glipizide – a short-acting sulphonylurea derivative. Przegl Lek 1996; 53
  • 4 Lebovitz HE. Glipizide: a second-generation sulfonylurea hypoglycemic agent. Pharmacology, pharmacokinetics and clinical use. Pharmacotherapy 1985; 5
  • 5 Kuhn T. The second generation oral sulfonylureas: glyburide and glipizide. Am Pharm. 1989: NS28
  • 6 Kidd RS, Straughn AB, Meyer MC et al. Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics. 1999; 9
  • 7 Tan B, Zhang YF, Chen XY et al. The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects. Eur J Clin Pharmacol 2010; 66
  • 8 Schror K. The pharmacology of cilostazol. Diabetes Obes Metab 2002; 4 (Suppl. 02)
  • 9 Chapman TM, Goa KL. Cilostazol: a review of its use in intermittent claudication. Am J Cardiovasc Drugs 2003; 3
  • 10 Akiyama H, Kudo S, Shimizu T. The metabolism of a new antithrombotic and vasodilating agent, cilostazol, in rat, dog and man. Arzneimittelforschung 1985; 35
  • 11 Bramer SL, Tata PN, Vengurlekar SS et al. Method for the quantitative analysis of cilostazol and its metabolites in human plasma using LC/MS/MS. J Pharm Biomed Anal 2001; 26
  • 12 Akiyama H, Kudo S, Odomi M et al. High-performance liquid chromatographic procedure for the determination of a new antithrombotic and vasodilating agent, cilostazol, in human plasma. J Chromatogr 1985; 338
  • 13 Emilsson H. High-performance liquid chromatographic determination of glipizide in human plasma and urine. J Chromatogr 1987; 421
  • 14 Tata PN, Fu CH, Browder NJ et al. The quantitative determination of cilostazol and its four metabolites in human liver microsomal incubation mixtures by high-performance liquid chromatography. J Pharm Biomed Anal 1998; 18
  • 15 Fu CJ, Tata PN, Okada K et al. Simultaneous quantitative determination of cilostazol and its metabolites in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1999; 728
  • 16 Tata PN, Fu CH, Bramer SL. Determination of cilostazol and its metabolites in human urine by high performance liquid chromatography. J Pharm Biomed Anal 2001; 24
  • 17 Ho EN, Yiu KC, Wan TS et al. Detection of anti-diabetics in equine plasma and urine by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 811
  • 18 Lin ZJ, Desai-Krieger D, Shum L. Simultaneous determination of glipizide and rosiglitazone unbound drug concentrations in plasma by equilibrium dialysis and liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 801
  • 19 Venkatesh P, Harisudhan T, Choudhury H et al. Simultaneous estimation of six anti-diabetic drugs – glibenclamide, gliclazide, glipizide, pioglitazone, repaglinide and rosiglitazone: development of a novel HPLC method for use in the analysis of pharmaceutical formulations and its application to human plasma assay. Biomed Chromatogr 2006; 20
  • 20 Ding CG, Zhou Z, Ge QH et al. Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography-tandem mass spectrometry. Biomed Chromatogr 2007; 21
  • 21 Varanasi KK, Sridhar V, Potharaju S et al. Development and validation of a liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of nateglinide, cilostazol and its active metabolite 3,4-dehydro-cilostazol in Wistar rat plasma and its application to pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 865
  • 22 Varanasi VS, Veeraraghavan S, Potharaju S et al. Validated high performance liquid chromatographic method for simultaneous determination of rosiglitazone, cilostazol, and 3,4-dehydro-cilostazol in rat plasma and its application to pharmacokinetics. Arzneimittelforschung 2008; 58
  • 23 Hess C, Musshoff F, Madea B. Simultaneous identification and validated quantification of 11 oral hypoglycaemic drugs in plasma by electrospray ionisation liquid chromatography-mass spectrometry. Anal Bioanal Chem. 2011