Details

Autor(en) / Beteiligte

• Pian, Phillip
• Labovitz, Edward
• Hoffman, Keith
• Clavijo, Claudia F.
• Rzasa Lynn, Rachael
• Galinkin, Jeffrey L.
• Vinks, Alexander A.
• Malik, Punam
• Christians, Uwe

Titel

Quantification of the 5-lipoxygenase inhibitor zileuton in human plasma using high performance liquid chromatography–tandem mass spectrometry

Ist Teil von

• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2013-10, Vol.937, p.79-83

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• •First reported development and validation of a clinical LC–MS/MS assay for zileuton.•The quantification range (3.05–20,000ng/mL) spans clinically relevant blood levels.•The assay reliably quantified zileuton in pediatric pharmacokinetic trials. Zileuton is an orally active, selective inhibitor of 5-lipoxygenase, which catalyzes the first step in the conversion of arachadonic acid into leukotrienes. Given the important role of leukotrienes in inflammation and cell signaling, multiple studies have investigated the efficacy of zileuton in the treatment of human disease. Examples of disease targets include asthma, ulcerative colitis, rheumatoid arthritis, and more recently, acne, ischemic/reperfusion injury, inflammatory pain, and sickle cell anemia. Zileuton is currently approved for the prophylaxis and chronic treatment of asthma. We report the development and validation of a sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay for the quantification of zileuton in human EDTA plasma. The range of reliable response was 3.05–20,000ng/mL in human plasma. The calibration curves had a correlation coefficient of r2>0.99. The intra-day precision was 3.4–5.3%. The inter-day precision ranged from 4.5% to 7.3% and inter-day accuracy from 100% to 107%. No matrix interferences, ion suppression/enhancement, or carry-over was observed. The assay met all predefined acceptance criteria and was subsequently employed to measure plasma zileuton concentrations in a clinical trial.