title: Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry.
abstract: Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with 0.4 mL of distilled water and 25 microL of a 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. The eluate was injected into a gas chromatography (GC) injector without evaporation and reconstitution steps, and was detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of the ten drugs from each other and from impurities was generally satisfactory using a DB-1MS column (30 m x 0.32 mm i.d., film thickness 0.25 microm). The recoveries of the ten antihistamines spiked into plasma were 73.8-105%. The regression equations for the ten antihistamines showed excellent linearity with detection limits of 0.02-5.0 ng/0.1 mL. The within-day and day-to-day coefficients of variation for plasma were not greater than 9.9%. The data obtained from determination of diphenhydramine and chlorpheniramine in human plasma after oral administration of the drugs are also presented.
authors.affiliation: Department of Legal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Hasegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kumazawa
authors.forename: Xiao-Pen
authors.initials: XP
authors.lastname: Lee
authors.forename: Masaya
authors.initials: M
authors.lastname: Fujishiro
authors.forename: Ayako
authors.initials: A
authors.lastname: Kuriki
authors.forename: Akemi
authors.initials: A
authors.lastname: Marumo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seno
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
mesh_terms: D000284:Administration, Oral; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D015394:Molecular Structure; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D006634:Histamine H1 Antagonists