Validation of an LC-MS/MS method for the quantitative determination of mavoglurant (AFQ056) in human plasma

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• 作者：Annamaria Jakab (1)
  Serge Winter (2)
  Marc Raccuglia (2)
  Frank Picard (3)
  Swati Dumitras (2)
  Ralph Woessner (2)
  Sanket Mistry (4)
  Jayraj Chudasama (4)
  Swati Guttikar (4)
  Olivier Kretz (2)
  
• 关键词：AFQ056 ; Mavoglurant ; mGluR5 ; LC ; MS/MS ; Human plasma ; Recovery ; Validation
• 刊名：Analytical and Bioanalytical Chemistry
• 出版年：2013
• 出版时间：January 2013
• 年：2013
• 卷：405
• 期：1
• 页码：215-223
• 全文大小：284KB
• 参考文献：1. Cole P (2012) Mavoglurant. Drugs Future 37:7-2
  2. Meldrum BS (2000) Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 130(4S, Suppl):1007S-015S
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  5. Levenga J, Hayashi S, de Vrij FM, Koekkoek SK, van der Linde HC, Nieuwenhuizen I, Song C, Buijsen RA, Pop AS, Gomez-Mancilla B, Nelson DL, Willemsen R, Gasparini F, Oostra BA (2011) AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome. Neurobiol Dis 42(3):311-17 CrossRef
  6. Gregoire L, Morin N, Ouattara B, Gasparini F, Bilbe G, Johns D, Vranesic I, Sahasranaman S, Gomez-Mancilla B, Di Paolo T (2011) The acute antiparkinsonian and antidyskinetic effect of AFQ056, a novel metabotropic glutamate receptor type 5 antagonist, in l -dopa-treated parkinsonian monkeys. Parkinsonism Relat Disord 17(4):270-76 CrossRef
  7. Berg D, Godau J, Trenkwalder C, Eggert K, Csoti I, Storch A, Gasparini F, Hariry S, Vandemeulebroecke M, Johns D, Gomez-Mancilla B (2010) AFQ056 treatment of severe levodopa- induced dyskinesias: proof of concept study. Mov Disord 25(suppl2):321 [14th Int Congr Parkinson’s Dis Mov Disord (June 13-7, Buenos Aires) 2010]
  8. Berg D, Godau J, Trenkwalder C, Eggert K, Csoti I, Storch A, Huber H, Morelli-Canelo M, Stamelou M, Ries V, Wolz M, Schneider C, Di Paolo T, Gasparini F, Hariry S, Vandemeulebroecke M, Abi-Saab W, Cooke K, Johns D, Gomez-Mancilla B (2011) AFQ056 treatment of levodopainduced dyskinesias: results of 2 randomized controlled trials. Mov Disord 26(7):1243-250 CrossRef
  9. Jacquemont S, Curie A, Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, Ramos FJ, Cornish K, He Y, Paulding C, Neri G, Chen F, Hadjikhani N, Martinet D, Meyer J, Beckmann JS, Delange K, Brun A, Bussy G, Gasparini F, Hilse T, Floesser A, Branson J, Bilbe G, Johns D, Gomez-Mancilla B (2011) Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med 3(64):64ra1 CrossRef
  10. Walles M, Wolf T, Gschwind HP, Krauser J, Woessner R, Chakraborty A, Ufer M, Swart P (2012) Absorption and disposition of mavoglurant (AFQ056) in healthy volunteers (The 19th International Symposium on Microsomes and Drug Oxidations and 12th European ISSX Meeting (June 17-1, 2012) P195
  11. Chakraborty A, Ufer M, Bhad P, Vandemeulebroecke M, Gomez-Mancilla B, Bell D, Winter S (2012) Lack of pharmacokinetic interaction between the novel mGluR5 antagonist AFQ056 and levodopa/carbidopa in healthy volunteers. Mov Disord 27(Suppl 1):456
  12. FDA guidance for industry, bioanalytical method validation, US department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) (2001)
  
• 作者单位：Annamaria Jakab (1)
  Serge Winter (2)
  Marc Raccuglia (2)
  Frank Picard (3)
  Swati Dumitras (2)
  Ralph Woessner (2)
  Sanket Mistry (4)
  Jayraj Chudasama (4)
  Swati Guttikar (4)
  Olivier Kretz (2)
  
  1. Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma AG., Fabrikstrasse 14, 3.02, 4056, Basel, Switzerland
  2. Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056, Basel, Switzerland
  3. Bioanalytics Division, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056, Basel, Switzerland
  4. Veeda Clinical Research Pvt. Ltd, Shivalik Plaza-A, Near I.I.M., Ambawadi, Ahmedabad, 380015, India
  
• ISSN：1618-2650

文摘

A simple, sensitive, and selective liquid chromatography/tandem mass spectrometry method was validated for the identification and quantification of mavoglurant (AFQ056) in human plasma. The chromatographic separation was performed using a Cosmosil 5 C18 (150?×-.6?mm, 5?μm) column at 40?±-.5?°C with a mobile phase consisting of acetic acid in water (0.1?%, v/v)/methanol (10:90, v/v) with a flow rate of 1.0?mL/min followed by quantification with tandem mass spectrometry, operating with electrospray ionization in positive ion mode and applying multiple reaction monitoring. The validated method described in this paper presents high absolute recovery with precision and accuracy meeting the acceptance criteria. The method was precise and accurate for 2- and 10-fold dilution of samples. The method was validated using sodium heparin as specific anticoagulant, and the anticoagulant effect was tested by lithium heparin and K3EDTA. The method was successfully cross-validated between two bioanalytical sites. The method was specific for mavoglurant within the given criteria for acceptance (apparent peak area at the retention time of mavoglurant in zero samples was less than 20?% compared with the mean peak area at LLOQ) in human plasma. The method was fully validated for the quantitative determination of mavoglurant in human plasma between the range of 2.00 and 2,500?ng/mL.