Automated 96-well solid phase extraction and hydrophilic interaction liquid chromatography–tandem mass spectrometric method for the analysis of cetirizine (ZYRTEC ®) in human plasma—with emphasis on method ruggedness

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2005-01, Vol.814 (1), p.105-114
• Main Authors: Song, Qi, Junga, Heiko, Tang, Yong, Li, Austin C., Addison, Tom, McCort-Tipton, Melanie, Beato, Brian, Naidong, Weng
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cetirizine; Cetirizine - blood; Chromatography, High Pressure Liquid - methods; Fundamental and applied biological sciences. Psychology; General pharmacology; HILIC–MS/MS; Histamine H1 Antagonists - blood; Humans; Mass Spectrometry - methods; Medical sciences; Method validation; Pharmacology. Drug treatments; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Synthesis of cetirizine-d 8
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2004.10.009

A high-throughput bioanalytical method based on automated sample transfer, automated solid phase extraction, and hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC–MS/MS) analysis, has been developed for the determination of cetirizine, a selective H 1-receptor antagonist. Deuterated cetirizine (cetirizine-d 8) was synthesized as described and was used as the internal standard. Samples were transferred into 96-well plates using an automated sample handling system. Automated solid phase extraction was carried out using a 96-channel programmable liquid-handling workstation. Solid phase extraction 96-well plate on polymer sorbent (Strata X) was used to extract the analyte. The extracted samples were injected onto a Betasil silica column (50 × 3, 5 μm) using a mobile phase of acetonitrile–water–acetic acid–trifluroacetic acid (93:7:1:0.025, v/v/v/v) at a flow rate of 0.5 ml/min. The chromatographic run time is 2.0 min per injection, with retention time of cetirizine and cetirizine-d 8 both at 1.1 min. The system consisted of a Shimadzu HPLC system and a PE Sciex API 3000 or API 4000 tandem mass spectrometer with (+) ESI. The method has been validated over the concentration range of 1.00–1000 ng/ml cetirizine in human plasma, based on a 0.10-ml sample size. The inter-day precision and accuracy of the quality control (QC) samples demonstrated