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Determination of memantine in human plasma by GC using negative ion chemical ionization MS detection after derivatization with a new reagent

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Abstract

We describe a method for the determination of memantine in plasma by use of the derivatization reagent o-(pentafluorobenzyloxycarbonyl)-benzoyl chloride. Memantine can be quantitatively analyzed down to 49 pg per mL of plasma using a 250 μL sample and negative ion chemical ionisation mass spectrometry (GC-NICI-MS). Plasma samples were made alkaline with carbonate buffer and extracted with n-hexane. The extracts were treated with reagent solution for 20 min, concentrated, and submitted to GC-NICI-MS. The method is rapid because extraction and derivatization occur in one single step. Amantadine is used as an internal standard. The utility and robustness of the assay is demonstrated by giving data on specificity, linearity, accuracy and precision, benchtop stability, freeze–thaw stability, autosampler stability, aliquot analysis, and prospective analytical batch size accuracy.

We describe a method for the determination of memantine in plasma by use of the derivatization reagent o-(pentafluorobenzyloxycarbonyl)-benzoyl chloride. Memantine can be quantitatively analyzed down to 49 pg per mL of plasma using a 250 μL sample and negative ion chemical ionisation mass spectrometry (GC-NICI-MS). Amantadine is used as an internal standard. The utility and robustness of the assay is demonstrated by giving data on specificity, linearity, accuracy and precision, benchtop stability, freeze–thaw stability, autosampler stability, aliquot analysis, and prospective analytical batch size accuracy.

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References

  1. Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacology 38(6):735–767

    Article  CAS  Google Scholar 

  2. Jarvis B, Figgitt DP (2003) Memantine. Drugs Aging 20(6):465–476, discussion 477–468

    Article  CAS  Google Scholar 

  3. Schneider E, Fischer PA, Clemens R, Balzereit F, Funfgeld EW, Haase HJ (1984) Effects of oral memantine administration on Parkinson symptoms. Results of a placebo-controlled multicenter study. Dtsch Med Wochenschr 109(25):987–990

    Article  CAS  Google Scholar 

  4. Ditzler K (1991) Efficacy and tolerability of memantine in patients with dementia syndrome. A double-blind, placebo controlled trial. Arzneimittelforsch/Drug Res 41(8):773–780

    CAS  Google Scholar 

  5. Kornhuber J, Weller M, Schoppmeyer K, Riederer P (1994) Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl 43:91–104

    CAS  Google Scholar 

  6. Danysz W, Parsons CG (2003) The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: preclinical evidence. Int J Geriatr Psychiatry 18(Suppl 1):S23–S32

    Article  Google Scholar 

  7. Robinson DM, Keating GM (2006) Memantine: a review of its use in Alzheimer’s disease. Drugs 66(11):1515–1534

    Article  CAS  Google Scholar 

  8. Lo D, Grossberg GT (2011) Use of memantine for the treatment of dementia. Expert Rev Neurother 11(10):1359–1370

    Article  CAS  Google Scholar 

  9. Wesemann W, Schollmeyer JD, Sturm G (1977) Gaschromatographic and mass spectrometric studies on metabolites of adamantane amines excreted with urine. Arzneimittelforsch/Drug Res 27(7):1471–1477

    CAS  Google Scholar 

  10. Wesemann W, Schollmeyer JD, Sturm G (1982) Distribution of memantine in brain, liver, and blood of the rat. Arzneimittelforsch/Drug Res 32(10):1243–1245

    CAS  Google Scholar 

  11. Suckow RF, Zhang MF, Collins ED, Fischman MW, Cooper TB (1999) Sensitive and selective liquid chromatographic assay of memantine in plasma with fluorescence detection after pre-column derivatization. J Chromatogr B: Biomed Sci Appl 729(1–2):217–224

    Article  CAS  Google Scholar 

  12. Shuangjin C, Fang F, Han L, Ming M (2007) New method for high-performance liquid chromatographic determination of amantadine and its analogues in rat plasma. J Pharm Biomed Anal 44(5):1100–1105

    Article  Google Scholar 

  13. Xie MF, Zhou W, Tong XY, Chen YL, Cai Y, Li Y, Duan GL (2011) High-performance liquid chromatographic determination of memantine hydrochloride in rat plasma using sensitive fluorometric derivatization. J Sep Sci 34(3):241–246

    Article  CAS  Google Scholar 

  14. Duh TH, Wu HL, Pan CW, Kou HS (2005) Fluorimetric liquid chromatographic analysis of amantadine in urine and pharmaceutical formulation. J Chromatogr A 1088(1–2):175–181

    CAS  Google Scholar 

  15. Toker SE, Sagirli O, Cetin SM, Onal A (2011) A new HPLC method with fluorescence detection for the determination of memantine in human plasma. J Sep Sci 34(19):2645–2649

    Article  CAS  Google Scholar 

  16. Higashi Y, Nakamura S, Matsumura H, Fujii Y (2006) Simultaneous liquid chromatographic assay of amantadine and its four related compounds in phosphate-buffered saline using 4-fluoro-7-nitro-2,1,3-benzoxadiazole as a fluorescent derivatization reagent. Biomed Chromatogr 20(5):423–428

    Article  CAS  Google Scholar 

  17. Puente B, Hernandez E, Perez S, Pablo L, Prieto E, Garcia MA, Bregante MA (2011) Determination of memantine in plasma and vitreous humour by HPLC with precolumn derivatization and fluorescence detection. J Chromatogr Sci 49(10):745–752

    Article  CAS  Google Scholar 

  18. Yeh HH, Yang YH, Chen SH (2010) Simultaneous determination of memantine and amantadine in human plasma as fluorescein derivatives by micellar electrokinetic chromatography with laser-induced fluorescence detection and its clinical application. Electrophoresis 31(11):1903–1911

    Article  CAS  Google Scholar 

  19. Almeida AA, Campos DR, Bernasconi G, Calafatti S, Barros FA, Eberlin MN, Meurer EC, Paris EG, Pedrazzoli J (2007) Determination of memantine in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to a bioequivalence study. J Chromatogr B 848(2):311–316

    Article  CAS  Google Scholar 

  20. Liu MY, Meng SN, Wu HZ, Wang S, Wei MJ (2008) Pharmacokinetics of single-dose and multiple-dose memantine in healthy chinese volunteers using an analytic method of liquid chromatography-tandem mass spectrometry. Clin Ther 30(4):641–653

    Article  CAS  Google Scholar 

  21. Noetzli M, Ansermot N, Dobrinas M, Eap CB (2012) Simultaneous determination of antidementia drugs in human plasma: procedure transfer from HPLC-MS to UPLC-MS/MS. J Pharm Biomed Anal 64–65:16–25

    Article  Google Scholar 

  22. Noetzli M, Choong E, Ansermot N, Eap CB (2011) Simultaneous determination of antidementia drugs in human plasma for therapeutic drug monitoring. Ther Drug Monit 33(2):227–238

    CAS  Google Scholar 

  23. Leis HJ, Fauler G, Windischhofer W (2002) Quantitative analysis of memantine in human plasma by gas chromatography/negative ion chemical ionization/mass spectrometry. J Mass Spectrom 37(5):477–480

    Article  CAS  Google Scholar 

  24. Leis HJ, Windischhofer W (2010) o-(Pentafluorobenzyloxycarbonyl)benzoyl chloride: a novel electrophoric derivatisation reagent for amino compounds designed for negative ion chemical ionisation mass spectrometry. Rapid Commun Mass Spectrom 24(22):3320–3324

    Article  CAS  Google Scholar 

  25. Leis H, Schütz H, Windischhofer W (2011) Quantitative determination of methylphenidate in plasma by gas chromatography negative ion chemical ionisation mass spectrometry using o-(pentafluorobenzyloxycarbonyl)-benzoyl derivatives. Anal Bioanal Chem 400(8):2663–2670

    Article  CAS  Google Scholar 

  26. Leis HJ, Fauler G, Raspotnig G, Windischhofer W (2000) Negative ion chemical ionization for the determination of methylphenidate in human plasma by stable isotope dilution gas chromatography/mass spectrometry. J Mass Spectrom 35(9):1100–1104

    Article  CAS  Google Scholar 

  27. Leis HJ, Fauler G, Raspotnig G, Windischhofer W (2000) Quantitative analysis of morphine in human plasma by gas chromatography-negative ion chemical ionization mass spectrometry. J Chromatogr B: Biomed Sci Appl 744(1):113–119

    Article  CAS  Google Scholar 

  28. Leis HJ, Leis M, Windischhofer W (1996) Stable isotope labelling and determination of ketroprofen in human plasma and urine by gas chromatography/negative ion chemical ionization mass spectrometry. J Mass Spectrom 31(5):486–492

    Article  CAS  Google Scholar 

  29. Leis HJ, Fauler G, Rechberger GN, Windischhofer W (2004) Electron-capture mass spectrometry: a powerful tool in biomedical trace level analysis. Curr Med Chem 11(12):1585–1594

    CAS  Google Scholar 

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  1. Research Unit of Osteology and Analytical Mass Spectrometry, University Hospital of Youth and Adolescence Medicine, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria

    Hans J. Leis & Werner Windischhofer

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  1. Hans J. Leis
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  2. Werner Windischhofer
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Correspondence to Hans J. Leis.

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Leis, H.J., Windischhofer, W. Determination of memantine in human plasma by GC using negative ion chemical ionization MS detection after derivatization with a new reagent. Microchim Acta 178, 309–314 (2012). https://doi.org/10.1007/s00604-012-0840-3

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  • DOI: https://doi.org/10.1007/s00604-012-0840-3

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