Chromatographia

, 70:1581 | Cite as

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

  • Jian-Jun Zou
  • Hong-Wei Fan
  • Da-Qing Guo
  • Ying-Bin Li
  • Song Lin
  • Yu-Bing Zhu
  • Cui-Xia Yu
  • Jie Zhou
  • Jiang-Hui Liu
  • Yun-Fang Hu
Original

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.

Keywords

Column liquid chromatography Tandem mass spectrometry Therapeutic drug monitoring Clopidogrel Clopidogrel carboxylic acid metabolite SR26334 

References

  1. 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 CrossRefGoogle Scholar
  2. 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 CrossRefGoogle Scholar
  3. 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 30:1288–1295CrossRefGoogle Scholar
  4. 4.
    Reist M, Vos RD, Montseny JP, Mayer JM, Carrupt PA, Berger Y, Testa B (2000) Drug Metab Dispos 28:1405–1410Google Scholar
  5. 5.
    Robinson A, Hillis J, Neal C, Leary AC (2007) J Chromatogr B 848:344–354. doi:10.1016/j.jchromb.2006.10.076 CrossRefGoogle Scholar
  6. 6.
    Lagorce P, Perez Y, Ortiz J, Necciari J, Bressolle F (1998) J Chromatogr B 720:107–117CrossRefGoogle Scholar
  7. 7.
    Singh SS, Sharma K, Barot D, Mohan PR, Lohray VB (2005) J Chromatogr B 821:173–180CrossRefGoogle Scholar
  8. 8.
    Souri E, Jalalizadeh H, Kebriaee-Zadeh A, Shekarchi M, Dalvandi A (2006) Biomed Chromatogr 20:1309–1314. doi:10.1002/bmc.697 CrossRefGoogle Scholar
  9. 9.
    Bahrami G, Mohammadi B, Sisakhtnezhad S (2008) J Chromatogr B 864:168–172CrossRefGoogle Scholar
  10. 10.
    Ksycinska H, Rudzki P, Bukowska-Kiliszek M (2006) J Pharm Biomed Anal 41:533–539. doi:10.1016/j.jpba.2005.11.035 CrossRefGoogle Scholar
  11. 11.
    Lainesse A, Ozalp Y, Wong H, Alpan RS (2004) Arzneimittel Forsch 54:600–604Google Scholar
  12. 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 CrossRefGoogle Scholar
  13. 13.
    Shin BS, Yoo SD (2007) Biomed Chromatogr 21:883–889. doi:10.1002/bmc.850 CrossRefGoogle Scholar
  14. 14.
    Taubert D, Kastrati A, Harlfinger S, Gorchakova O, Lazar A, Beckerath N, Schomig A, Schomig E (2004) Thromb Haemostasis 92:311–316Google Scholar
  15. 15.
    Mani H, Toennes SW, Linnemann B, Urbanek DA, Schwonberg J, Kauert GF, Lindhoff-Last E (2008) Ther Drug Monit 30:84–89CrossRefGoogle Scholar
  16. 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 BPGoogle Scholar
  17. 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 24:1962–1973Google Scholar
  18. 18.
    Krouwer JS, Rabinowitz R (1984) Clin Chem 30:290–292Google Scholar

Copyright information

© Vieweg+Teubner | GWV Fachverlage GmbH 2009

Authors and Affiliations

  • Jian-Jun Zou
    • 1
  • Hong-Wei Fan
    • 1
  • Da-Qing Guo
    • 2
  • Ying-Bin Li
    • 3
  • Song Lin
    • 4
  • Yu-Bing Zhu
    • 1
  • Cui-Xia Yu
    • 1
  • Jie Zhou
    • 1
  • Jiang-Hui Liu
    • 1
  • Yun-Fang Hu
    • 1
  1. 1.Department of Clinical Pharmacology, Nanjing First HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.Department of Pharmacy, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Department of Neurosurgery, Nanjing First HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  4. 4.Department of Cardiology, Nanjing First HospitalNanjing Medical UniversityNanjingPeople’s Republic of China

Personalised recommendations