PII‐80

BACKGROUND/AIMS To evaluate the sensitivity of ifosfamide (IFF) and its 2‐ and 3‐N‐dechloroethylated metabolites (2‐DCE‐IFF and 3‐DCE‐IFF) using ES interface vs. APCI interface in LC/MS methods. METHODS Standard calibration curves were prepared by spiking an aliquot of 0.025 ml of standard containing ifosfamide, 2‐DCE‐IFF and 3‐DCE‐IFF into 0.1 ml drug‐free human plasma, then liquid/liquid extracted with 3 ml of ethyl acetate. The resulting organic phase was evaporated to dryness and reconstituted in 0.5 ml methanol and 0.010 ml was injected. Enantioselective separations were achieved using a C18 column (4.6 × 150 mm) and a Chirobiotic T column (4.6 × 150 mm). The mobile phase was 2‐propanol: NH4OAc (10 mM, pH 7.0) and a gradient from 5% to 18% 2‐propanol, a flow rate of 0.5 ml/min. The detection and quantification of the compounds were achieved using selected‐ion monitoring at m/z=261.1 for IFF and m/z=199.1 for the 2‐DCE‐IFF and 3‐DCE‐IFF. RESULTS Linear relationships between peak height and drug concentrations were obtained for all the analytes using each of the two interfaces separately (ES vs APCI): IFF showed a linear response in the range of 100–4000 ng/ml (LLOQ=100 ng/ml) in ES, versus 3–4000 ng/ml (LLOQ=3 ng/ml) in APCI. For 2‐DCE‐IFF from 50–2000 ng/ml in both interfaces. For 3‐DCE‐IFF from 6–4000 ng/ml in both interfaces. CONCLUSIONS IFF showed better sensitivity using APCI than ES (ratio APCI:ES = 32:1). No difference in sensitivity was found for 2‐DCE‐IFF and 3‐DCE‐IFF metabolites. Clinical Pharmacology & Therapeutics (2005) 79 , P57–P57; doi: 10.1016/j.clpt.2005.12.205