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논문 기본 정보

자료유형
학술저널
저자정보
Shin, Young G. (Drug Metabolism and Pharmacokinetics, Genentech Inc.) Lee, Hamm (Alta Analytical Laboratory, Intertek Pharmaceutical Services) Murakami, Stanley (Alta Analytical Laboratory, Intertek Pharmaceutical Services) Buirst, Kenji (Alta Analytical Laboratory, Intertek Pharmaceutical Services) Buonarati, Michael H. (Alta Analytical Laboratory, Intertek Pharmaceutical Services) Cox, April (Array Biopharma Inc.) Regal, Kelly (Array Biopharma Inc.) Hunt, Kevin W. (Array Biopharma Inc.) Scearce-Levie, Kimberly (Drug Metabolism and Pharmacokinetics, Genentech Inc.) Watts, Ryan J. (Drug Metabolism and Pharmacokinetics, Genentech Inc.) Liu, Xingrong (Drug Metabolism and Pharmacokinetics, Genentech Inc.)
저널정보
대한약학회 Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 제37권 제5호
발행연도
2014.1
수록면
636 - 644 (9page)

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A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and applied for the determination of human $A{\beta}1$-40 and $A{\beta}1$-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. $^{15}N_{53}-A{\beta}1$-40 and $^{15}N_{55}-A{\beta}1$-42 peptides were used as internal standards. A quadratic regression (weighted 1/concentrations), with an equation $y=ax^2+bx+c$, was used to fit calibration curves over the concentration range of 0.500-100 ng/mL for both $A{\beta}1$-40 and $A{\beta}1$-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 ${\geq}8.23%$ for $A{\beta}1$-40. Within-run accuracy ranged from -4.83 to 10.1 % with precision values ${\geq}8.87%$ for $A{\beta}1$-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 $A{\beta}1$-40 quantification of samples from the Tg2576 amyloid precursor protein transgenic mouse model, but varied slightly for $A{\beta}1$-42.

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