Quantitative determination of cetirizine enantiomers in guinea pig plasma, brain tissue and microdialysis samples using liquid chromatography/tandem mass spectrometry

• Published in: Rapid communications in mass spectrometry 2005-01, Vol.19 (12), p.1749-1757
• Main Authors: Gupta, Anubha, Jansson, Britt, Chatelain, Pierre, Massingham, Roy, Hammarlund-Udenaes, Margareta
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Brain Chemistry; Cetirizine - analogs & derivatives; Cetirizine - blood; Cetirizine - pharmacokinetics; Chromatography, High Pressure Liquid; FARMACI; Guinea Pigs; Histamine H1 Antagonists, Non-Sedating - blood; Histamine H1 Antagonists, Non-Sedating - pharmacokinetics; Microdialysis; PHARMACY; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization - methods; Stereoisomerism
• ISSN: 0951-4198; 1097-0231; 1097-0231
• DOI: 10.1002/rcm.1983

Sensitive enantioselective liquid chromatographic assays using tandem mass spectrometric detection were developed and validated for the determination of S‐cetirizine (S‐CZE) and R‐cetirizine (R‐CZE) in guinea pig plasma, brain tissue, and microdialysis samples. Enantioselective separation was achieved on an α1‐acid glycoprotein column within 14 min for all methods. A cetirizine analog, ucb 20028, was used as internal standard. Cetirizine and the internal standard were detected by multiple reaction monitoring using transitions m/z 389.1 → 200.9 and 396.1 → 276.1, respectively. The samples were prepared using protein precipitation with acetonitrile. For guinea pig plasma, the assay was linear over the range 0.25–5000 ng/mL for both S‐CZE and R‐CZE, with a lower limit of quantification (LLOQ) of 0.25 ng/mL. For the brain tissue and microdialysis samples, the assays were linear over the range 2.5–250 ng/g and 0.25–50 ng/mL, respectively, and the LLOQ values were 2.5 ng/g and 0.25 ng/mL, respectively. The intra‐ and inter‐day precision values were ≤7.1% and ≤12.6%, respectively, and the intra‐ and inter‐day accuracy varied by less than ±8.0% and ±6.0% of the nominal value, respectively, for both enantiomers in all the matrices investigated. Copyright © 2005 John Wiley & Sons, Ltd.