Microdose clinical trial: Quantitative determination of fexofenadine in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 858; no. 1; pp. 118 - 128
• Main Authors: Yamane, Naoe, Tozuka, Zenzaburou, Sugiyama, Yuichi, Tanimoto, Toshiko, Yamazaki, Akira, Kumagai, Yuji
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-10-2007; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Anti-Allergic Agents - administration & dosage; Anti-Allergic Agents - blood; Anti-Allergic Agents - pharmacokinetics; Biological and medical sciences; Calibration; Chromatography, Liquid - methods; Electrospray ionization; Fexofenadine; Fundamental and applied biological sciences. Psychology; General pharmacology; Humans; Medical sciences; Microdosing; Molecular Structure; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Reproducibility of Results; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization - methods; Tandem mass spectrometry; Tandem Mass Spectrometry - methods; Terfenadine - administration & dosage; Terfenadine - analogs & derivatives; Terfenadine - blood; Terfenadine - pharmacokinetics; Validation; Validation; Tandem mass spectrometry; Fexofenadine; Electrospray ionization; Microdosing; Human; Biological fluid; Antihistaminic; Electrospray; Blood plasma; Mass spectrometry MS/MS; Clinical trial; Antagonist; H1 Histamine receptor; Quantitative analysis
• DOI: 10.1016/j.jchromb.2007.08.011
• EISSN: 1873-376X
• ISSN: 1570-0232

A sample treatment procedure and high-sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for quantitative determination of fexofenadine in human plasma was developed for a microdose clinical trial with a
cold drug, i.e., a non-radioisotope-labeled drug. Fexofenadine and terfenadine, as internal standard, were extracted from plasma samples using a 96-well solid-phase extraction plate (Oasis HLB). Quantitation was performed on an ACQUITY UPLC system and an API 5000 mass spectrometer by multiple reaction monitoring. Chromatographic separation was achieved on an XBridge C18 column (100
mm
×
2.1
mm i.d., particle size 3.5
μm) using acetonitrile/2
mM ammonium acetate (91:9, v/v) as the mobile phase at a flow rate of 0.6
ml/min. The analytical method was validated in accordance with the FDA guideline for validation of bioanalytical methods. The calibration curve was linear in the range of 10–1000
pg/ml using 200
μl of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 1–500
ng/ml using 20
μl of plasma, was also conducted. Each method was successfully applied for making determinations in plasma using LC/ESI-MS/MS after administration of a microdose (100
μg solution) and a clinical dose (60
mg dose) in eight healthy volunteers.