Validation of a sensitive and automated 96-well solid-phase extraction liquid chromatography–tandem mass spectrometry method for the determination of desloratadine and 3-hydroxydesloratadine in human plasma

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 792; no. 2; pp. 229 - 240
• Main Authors: Yang, Liyu, Clement, Robert P, Kantesaria, Bhavna, Reyderman, Larisa, Beaudry, Francis, Grandmaison, Charles, Di Donato, Lorella, Masse, Robert, Rudewicz, Patrick J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.07.2003; Elsevier Science
• Subjects: 3-Hydroxydesloratadine; Analysis; Automation; Biological and medical sciences; Calibration; Chromatography, Liquid - methods; Desloratadine; General pharmacology; Humans; Loratadine - analogs & derivatives; Loratadine - blood; Mass Spectrometry - methods; Medical sciences; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity; 3-Hydroxydesloratadine; Desloratadine; Human; Validation; Solid phase extraction; Biological fluid; Mass spectrometry MS/MS; Environmental factor; Liquid chromatography; Quantitative analysis; Blood plasma
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/S1570-0232(03)00267-8

To support clinical development, a liquid chromatographic–tandem mass spectrometric (LC–MS–MS) method was developed and validated for the determination of desloratadine (descarboethoxyloratadine) and 3-OH desloratadine (3-hydroxydescarboethoxyloratadine) concentrations in human plasma. The method consisted of automated 96-well solid-phase extraction for sample preparation and liquid chromatography/turbo ionspray tandem mass spectrometry for analysis. [ 2H 4]Desloratadine and [ 2H 4]3-OH desloratadine were used as internal standards (I.S.). A quadratic regression (weighted 1/concentration 2) gave the best fit for calibration curves over the concentration range of 25–10 000 pg/ml for both desloratadine and 3-OH desloratadine. There was no interference from endogenous components in the blank plasma tested. The accuracy (%bias) at the lower limit of quantitation (LLOQ) was −12.8 and +3.4% for desloratadine and 3-OH desloratadine, respectively. The precision (%CV) for samples at the LLOQ was 15.1 and 10.9% for desloratadine and 3-OH desloratadine, respectively. For quality control samples at 75, 1000 and 7500 pg/ml, the between run %CV was ≤7.5% for desloratadine and ≤6.3% for 3-OH desloratadine. Between run %bias ranged from 4.1 to 8.0% for desloratadine and −11.5 to −4.8% for 3-OH desloratadine. Desloratadine and 3-OH desloratadine were stable in human plasma for 401 days at −22 °C, after five freeze/thaw cycles, up to 24 h at room temperature, and in reconstituted sample extracts (up to 185 h at 5 °C). This LC–MS–MS method for the determination of desloratadine and 3-OH desloratadine in human plasma met regulatory requirements for selectivity, sensitivity, goodness of fit, precision, accuracy and stability.