Validation of an LC-MS/MS method for the quantitative determination of mavoglurant (AFQ056) in human plasma.
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 × 4.6 mm, 5 μm) column at 40 ± 0.5 °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 K(3)EDTA. 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.
Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma AG., Fabrikstrasse 14, 3.02, 4056 Basel, Switzerland. annamaria.jakab@novartis.com
Annamaria
A
Jakab
Serge
S
Winter
Marc
M
Raccuglia
Frank
F
Picard
Swati
S
Dumitras
Ralph
R
Woessner
Sanket
S
Mistry
Jayraj
J
Chudasama
Swati
S
Guttikar
Olivier
O
Kretz
D000925:Anticoagulants / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006493:Heparin / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000032:analysis* / Q000097:blood; D007477:Ions; D008956:Models, Chemical; D010949:Plasma / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D000925:Anticoagulants; D007211:Indoles; D007477:Ions; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D006493:Heparin; C581397:mavoglurant