Determination of mequitazine in human plasma by gas-chromatography/mass spectrometry with ion-trap detector and its pharmacokinetics after oral administration to volunteers.
The objective of this study was to develop an assay for mequitazine (MQZ) for the study of the bioavailability of the drug in human subjects. Using one mL of human plasma, the pH of the sample was adjusted and MQZ in the aqueous phase extracted with hexane; the organic layer was then evaporated to dryness, reconstituted and an aliquot introduced to a gas chromatograph/mass spectrometer (GC/MS) system with ion-trap detector. Inter- and intra-day precision of the assay were less than 15.1 and 17.7%, respectively; Inter- and intra-day accuracy were less than 8.91 and 18.6 %, respectively. The limit of quantification for the current assay was set at 1 ng/mL. To determine whether the current assay is applicable in a pharmacokinetic study for MQZ in human, oral formulation containing 10 mg MQZ was administered to healthy male subjects and blood samples collected. The current assay was able to quantify MQZ levels in most of the samples. The maximum concentration (Cmax) was 8.5 ng/mL, which was obtained at 10.1 h, with mean half-life of approximately 45.5 h. Under the current sampling protocol, the ratio of AUCt-->last to AUCt-->infinity was 93.4%, indicating that the blood collection time of 216 h is reasonable for MQZ. Therefore, these observations indicate that an assay for MQZ in human plasma is developed by using GC/MS with ion-trap detector and validated for the study of pharmacokinetics of single oral dose of 10 mg MQZ, and that the current study design for the bioavailability study is adequate for the drug.
Kwon
Oh-Seung
OS
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, Seoul, Korea. oskwon@kist.re.kr
Kim
Hye-Jung
HJ
Pyo
Heesoo
H
Chung
Suk-Jae
SJ
Chung
Youn Bok
YB
D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006634:Histamine H1 Antagonists / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010640:Phenothiazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
D006634:Histamine H1 Antagonists; D010640:Phenothiazines; D012997:Solvents; C006069:mequitazine