Liquid chromatographic-tandem mass spectrometric method for the determination of the neuraminidase inhibitor zanamivir (GG167) in human serum.
An LC-MS-MS method for the analysis of the neuraminidase inhibitor, zanamivir, in human serum is described. Zanamivir was extracted from protein precipitated human serum samples using Isolute SCX solid-phase extraction cartridges and analysed using reversed-phase chromatography with TurboIonSpray atmospheric pressure ionisation followed by mass spectrometric detection. The method uses a stable isotope internal standard, is highly specific and sensitive for a compound of this type and has been used for the analysis of human serum and urine samples from clinical studies. The method was extended to the analysis of serum and plasma samples from pre-clinical studies involving the rat, ferret and cell culture media. The method has been shown to be robust and valid over a concentration range of 10-5000 ng/ml using a 0.2-ml sample volume. The main advantages of this method compared to earlier procedures are primarily specificity, sensitivity, ease of sample preparation, small sample volume and short analysis time (ca. 5 min).
Allen
G D
GD
Department of Mass Spectrometry, Division of Drug Metabolism and Pharmacokinetics, Huntingdon Life Sciences, Cambridgeshire, UK.
Brookes
S T
ST
Barrow
A
A
Dunn
J A
JA
Grosse
C M
CM
D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood; D006146:Guanidines; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011714:Pyrans; D011786:Quality Control; D051381:Rats; D015203:Reproducibility of Results; D012794:Sialic Acids / Q000097:blood*; D053243:Zanamivir
D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D009439:Neuraminidase; D053243:Zanamivir