Analytical validation of accelerator mass spectrometry for pharmaceutical development.

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).

Accelerator mass spectrometry best practices for accuracy and precision in bioanalytical (14)C measurements.

Accelerator mass spectrometers have an energy acceleration and charge exchange between mass definition stages to destroy molecular isobars and allow single ion counting of long-lived isotopes such as (14)C (t½=5370 years.). 'Low' voltage accelerations to 200 kV allow laboratory-sized accelerator mass spectrometers instruments for bioanalytical quantitation of (14)C to 2-3% precision and accuracy in isolated biochemical fractions.

Early human ADME using microdoses and microtracers: bioanalytical considerations.

Quantitative assessment of metabolites of drug candidates in early-phase clinical development presents an analytical challenge when methods, standards and assays are not yet available. Radioisotopic labeling, principally with radiocarbon ((14)C), is the preferred method for discovering and quantifying the absolute yields of metabolites in the absence of reference material or a priori knowledge of the human metabolism. However, the detection of (14)C is inefficient by decay counting methods and, as a result, high radiological human (14)C-doses had been needed to assure sensitive detection of metabolites over time.

Modifications of the human urocortin 2 peptide that improve pharmacological properties.

Recently, we demonstrated that the corticotropin releasing factor 2 receptor agonist, urocortin 2, demonstrated anti-atrophy effects in rodent skeletal muscle atrophy models. Compared to other CRF2R agonists however, the in vivo pharmacological potency of urocortin 2 is poor when it is administered by continuous subcutaneous infusion. Therefore, we attempted to modify the structure of urocortin 2 to improve in vivo efficacy when administered by subcutaneous infusion.