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KMID : 0043320140370050636
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Archives of Pharmacal Research
2014 Volume.37 No. 5 p.636 ~ p.644
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Qualification and application of a liquid chromatography?tandem mass spectrometric method for the determination of human Aβ1-40 and Aβ1-42 peptides in transgenic mouse plasma using micro-elution solid phase extraction
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Shin Young-G.
Hamm Lee
Murakami Stanley
Buirst Kenji
Buonarati Michael H.
Cox April
Regal Kelly
Hunt Kevin W.
Scearce Levie Kimberly
Watts Ryan J.
Liu Xingrong
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Abstract
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A liquid chromatographic?tandem mass spectrometric (LC?MS/MS) method was developed and applied for the determination of human Aβ1-40 and Aβ1-42 peptides in transgenic mouse plasma to support preclinical pharmacodynamics studies. The method consisted of micro-elution solid phase extraction for sample preparation and LC?MS/MS analysis in the negative ion mode using electrospray ionization for analysis. 15N53-Aβ1-40 and 15N55-Aβ1-42 peptides were used as internal standards. A quadratic regression (weighted 1/concentrations), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range of 0.500?100 ng/mL for both Aβ1-40 and Aβ1-42 peptides. For quality control samples at 6.00, 40.0 and 80.0 ng/mL from the qualification experiment, the within-run accuracy ranged from ?2.69 to 0.583 % with precision values ≤8.23 % for Aβ1-40. Within-run accuracy ranged from ?4.83 to 10.1 % with precision values ≤8.87 % for Aβ1-42. Samples from a pharmacodynamics study using Tg2576 transgenic mice were analyzed by this qualified LC?MS/MS method and concentrations were compared to those generated by ELISA. The two methods were shown to be comparable for Aβ1-40 quantification of samples from the Tg2576 amyloid precursor protein transgenic mouse model, but varied slightly for Aβ1-42.
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KEYWORD
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Alzheimer disease, Human Aβ1-40, Aβ1-42, LC?MS analysis, ELISA, Tg2576 mouse plasma
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