Turbulent flow and ternary column-switching on-line clean-up system for high-throughput quantification of risperidone and its main metabolite in plasma by LC-MS/MS Application to a bioequivalence study

• Published in: Talanta (Oxford) 2007-04, Vol.72 (2), p.360-367
• Main Authors: KOUSOULOS, Constantinos, DOTSIKAS, Yannis, LOUKAS, Yannis L
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Chemistry; Chromatographic methods and physical methods associated with chromatography; Exact sciences and technology; Other chromatographic methods; Spectrometric and optical methods
• ISSN: 0039-9140; 1873-3573
• DOI: 10.1016/j.talanta.2006.10.049

A high-throughput LC-MS/MS method was developed for the simultaneous determination of Risperidone and 9-OH-risperidone in human plasma. A semi-automated sample preparation procedure was applied, including protein precipitation after addition of ACN, via a robotic system, and subsequent sub-zero temperature extraction of the latter. Injections of the ACN extractants were performed on a turbulent flow ternary column-switching system, consisted of dual extraction columns in parallel for on-line purification of samples and an analytical column. Toggling with the assistance of two valves provided a run cycle time of 3 min and the whole procedure minimized carry-over effect. On-line clean-up procedure along with sub-zero temperature extraction increased sample purification and extended column life. The analytical range of the method was 0.1-200 ng mL(-1) for both analytes with excellent linearity and very good accuracy and precision. The proposed method was employed in a bioequivalence study after per os administration of a 2mg tablet of risperidone and allowed the completion of the study (>1400 samples) in only 4 days time.