Elderly patients showed increased AUC/D and reduced total Cl compared to young adult patients due to the age-related reduced renal function. Differences in the PK-PD properties of rocuronium in elderly population are due to changes in drug disposition rather than to alterations in the sensitivity to the drug.

The ribonucleotide reductase inhibitor and radiosensitizer triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), NSC 663249) is clinically being evaluated via the intravenous (IV) route for the treatment of cervical and vulvar cancer in combination with primary cisplatin chemoradiation. The need for a 2-h infusion and frequent administration of triapine is logistically challenging, prompting us to pursue oral (PO) administration. In support of the clinical trial investigating oral triapine in combination with chemoradiation, we developed and validated a novel LC-MS/MS assay for the quantification of triapine in 50 μL human plasma. After protein precipitation, chromatographic separation of the supernatant was achieved with a Shodex ODP2 column and an isocratic acetonitrile-water mobile phase with 10% ammonium acetate. Detection with an ABI 4000 mass spectrometer utilized electrospray positive mode ionization. The assay was linear from 3–3,000 ng/mL and proved to be accurate (97.1-103.1%) and precise (<7.4%CV), and met the U.S. FDA guidance for bioanalytical method validation. This LC-MS/MS assay will be an essential tool to further define the pharmacokinetics and oral bioavailability of triapine.