Laquinimod (ABR-215062) is a synthetic compound currently undergoing clinical development for oral treatment of multiple sclerosis. The present paper describes the development, validation and clinical application of two rapid and sensitive methods for the determination of ABR-215062 in human plasma. Both methods use liquid chromatography/tandem mass spectrometry (LC/MS/MS) with electrospray ionization in positive mode and a stable isotope (13C6)-labeled ABR-215062 as internal standard for calibration. The selected reaction monitoring was based on the transitions m/z 357.1 → 236.1 for ABR-215062, and either m/z 363.2 → 236.1 or 365.2 → 238.1 for 13C6-ABR-215062. Method 1, aimed and validated for low level determinations (0.4–100 nmol/L) of ABR-215062, utilizes solid-phase extraction followed by isocratic elution. Method 2, aimed and validated for wide range determinations (0.75–15000 nmol/L) of ABR-215062, utilizes protein precipitation followed by fast gradient elution. The methods were validated with respect to selectivity, lower limit of quantification (LLOQ), dynamic range, precision, accuracy, extraction recovery and ruggedness. Furthermore, the stability of low level ABR-215062 in plasma was investigated. The methods were also applied in clinical trials. The LLOQs were 0.4 and 0.75 nmol/L for methods 1 and 2, respectively. The intra- and inter-day precision for the methods were 1.6–3.5% and 2.1–5.7%. The extraction recoveries were 90–97% for both methods. ABR-215062 was stable in plasma for at least 3 months when stored at −20°C. In conclusion, our developed methods were found to be selective, sensitive, robust and suitable for applications in clinical pharmacokinetic profiling. Copyright © 2006 John Wiley & Sons, Ltd.
If you can't find a tool you're looking for, please click the link at the top of the page to "Go to old article view". Alternatively, view our Knowledge Base articles for additional help. Your feedback is important to us, so please let us know if you have comments or ideas for improvement.