Determination of the immunomodulator laquinimod in human plasma by liquid chromatography/tandem mass spectrometry; development, validation and application of two methods in clinical pharmacokinetic profiling.

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 degrees 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.) -->
Substance Nomenclature: 0 (Immunologic Factors)
0 (Quinolones)
908SY76S4G (laquinimod)
Entry Date(s): Date Created: 20061018 Date Completed: 20070119 Latest Revision: 20191210
Update Code: 20231215
DOI: 10.1002/rcm.2730
PMID: 17044118
Autor: Sennbro CJ; Research and Development Laboratories, Active Biotech Research AB, Box 724, SE-22007 Lund, Sweden. carl-johan.sennbro@activebiotech.com, Olin M, Edman K, Hansson G, Gunnarsson PO, Svensson LD
Jazyk: angličtina
Zdroj: Rapid communications in mass spectrometry : RCM [Rapid Commun Mass Spectrom] 2006; Vol. 20 (22), pp. 3313-8.
DOI: 10.1002/rcm.2730
Abstrakt: 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 degrees 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.)
Databáze: MEDLINE
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