title: Analytical validation of accelerator mass spectrometry for pharmaceutical development.
abstract: The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of (14)C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the (14)C label), stable across samples storage conditions for at least 1 year, linear over four orders of magnitude with an analytical range from 0.1 Modern to at least 2000 Modern (instrument specific). Furthermore, accuracy was excellent (between 1 and 3%), while precision expressed as coefficient of variation was between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of (14)C, respectively (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with (14)C corresponds to 30 fg equivalents. Accelerator mass spectrometry provides a sensitive, accurate and precise method of measuring drug compounds in biological matrices.
authors.affiliation: Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason OH 45040, USA.
authors.forename: Bradly D
authors.initials: BD
authors.lastname: Keck
authors.forename: Ted
authors.initials: T
authors.lastname: Ognibene
authors.forename: John S
authors.initials: JS
authors.lastname: Vogel
mesh_terms: D000818:Animals; D004340:Drug Contamination; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D004364:Pharmaceutical Preparations