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Simultaneous Determination of Clopidogrel and Its Carboxylic Acid Metabolite (SR26334) in Human Plasma by LC–ESI–MS–MS: Application to the Therapeutic Drug Monitoring of Clopidogrel

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Abstract

A sensitive and specific liquid chromatography-tandem-mass spectrometry method was developed and validated for the simultaneous determination of clopidogrel and its carboxylic acid metabolite (SR26334) in human plasma using nateglinide and pioglitazone as internal standards. Analytes were extracted from 0.50 mL of plasma using diethyl ether–n-hexane (4:1, v/v). Chromatographic separation was performed on a Teknokroma C18 column with a mobile phase of methanol–water (containing 0.1% formic acid) (80:20, v/v) at a flow rate of 0.20 mL min−1 within 5.6 min. Linearity was established over the concentration range of 0.005–5 ng mL−1 for clopidogrel and 20–2,500 ng mL−1 for SR26334. Intra- and inter-batch standard deviations were less than 9.2% and the accuracy of this assay was found to fall within an acceptable range ≤10.0%. The method was successfully applied to the therapeutic drug monitoring of clopidogrel.

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References

  1. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS (2008) New Engl J Med 360:354–362. doi:10.1056/nejmoa0809171

    Article  Google Scholar 

  2. Simon T, Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg PG, Ferrieres J, Danchin N, Becquemont L (2008) New Engl J Med 360:363–375. doi:10.1056/NEJMoa0808227

    Article  Google Scholar 

  3. Pereillo JM, Maftouh M, Andrieu A, Uzabiaga MF, Fedeli O, Savi P, Pascal M, Herbert JM, Maffrand JP, Picard C (2002) Drug Metab Dispos 30:1288–1295

    Article  CAS  Google Scholar 

  4. Reist M, Vos RD, Montseny JP, Mayer JM, Carrupt PA, Berger Y, Testa B (2000) Drug Metab Dispos 28:1405–1410

    CAS  Google Scholar 

  5. Robinson A, Hillis J, Neal C, Leary AC (2007) J Chromatogr B 848:344–354. doi:10.1016/j.jchromb.2006.10.076

    Article  CAS  Google Scholar 

  6. Lagorce P, Perez Y, Ortiz J, Necciari J, Bressolle F (1998) J Chromatogr B 720:107–117

    Article  CAS  Google Scholar 

  7. Singh SS, Sharma K, Barot D, Mohan PR, Lohray VB (2005) J Chromatogr B 821:173–180

    Article  CAS  Google Scholar 

  8. Souri E, Jalalizadeh H, Kebriaee-Zadeh A, Shekarchi M, Dalvandi A (2006) Biomed Chromatogr 20:1309–1314. doi:10.1002/bmc.697

    Article  CAS  Google Scholar 

  9. Bahrami G, Mohammadi B, Sisakhtnezhad S (2008) J Chromatogr B 864:168–172

    Article  CAS  Google Scholar 

  10. Ksycinska H, Rudzki P, Bukowska-Kiliszek M (2006) J Pharm Biomed Anal 41:533–539. doi:10.1016/j.jpba.2005.11.035

    Article  CAS  Google Scholar 

  11. Lainesse A, Ozalp Y, Wong H, Alpan RS (2004) Arzneimittel Forsch 54:600–604

    CAS  Google Scholar 

  12. Nirogi RV, Kandikere VN, Shukla M, Mudigonda K, Maurya S, Boosi R (2006) Rapid Commun Mass Spectrom 20:1695–1700. doi:10.1002/rcm.2497

    Article  CAS  Google Scholar 

  13. Shin BS, Yoo SD (2007) Biomed Chromatogr 21:883–889. doi:10.1002/bmc.850

    Article  CAS  Google Scholar 

  14. Taubert D, Kastrati A, Harlfinger S, Gorchakova O, Lazar A, Beckerath N, Schomig A, Schomig E (2004) Thromb Haemostasis 92:311–316

    CAS  Google Scholar 

  15. Mani H, Toennes SW, Linnemann B, Urbanek DA, Schwonberg J, Kauert GF, Lindhoff-Last E (2008) Ther Drug Monit 30:84–89

    Article  CAS  Google Scholar 

  16. Guidance for Industry Bioanalytical Method Validation US Department of Health and Human Services Food and Drug Administration Centre for Drug Evaluation and Research (CDER) Centre for Veterinary Medicine (CVM) May 2001 BP

  17. Viswanathan CT, Bansal S, Booth B, DeStefano AJ, Rose MJ, Sailstad J, Shah VP, Skelly JP, Swann PG, Weiner R (2007) Arch Pharm Res 24:1962–1973

    CAS  Google Scholar 

  18. Krouwer JS, Rabinowitz R (1984) Clin Chem 30:290–292

    CAS  Google Scholar 

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Correspondence to Hong-Wei Fan.

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Zou, JJ., Fan, HW., Guo, DQ. et al. Simultaneous Determination of Clopidogrel and Its Carboxylic Acid Metabolite (SR26334) in Human Plasma by LC–ESI–MS–MS: Application to the Therapeutic Drug Monitoring of Clopidogrel. Chroma 70, 1581–1586 (2009). https://doi.org/10.1365/s10337-009-1349-8

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  • DOI: https://doi.org/10.1365/s10337-009-1349-8

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