Determination of dextromethorphan in human plasma using pipette tip solid-phase extraction and gas chromatography–mass spectrometry

• Published in: Analytical and bioanalytical chemistry Vol. 401; no. 7; pp. 2215 - 2223
• Main Authors: Hasegawa, Chika, Kumazawa, Takeshi, Uchigasaki, Seisaku, Lee, Xiao-Pen, Sato, Keizo, Terada, Masaru, Kurosaki, Kunihiko
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.10.2011; Springer
• Subjects: Administration, Oral; Analytical Chemistry; Biochemistry; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Chromatographic methods and physical methods associated with chromatography; Dextromethorphan; Dextromethorphan - administration & dosage; Dextromethorphan - blood; Dispensing; Exact sciences and technology; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - blood; Food Science; Gas chromatographic methods; Gas chromatography; Gas Chromatography-Mass Spectrometry; Glycine; Human; Humans; Hydroxides; Ionization; Laboratory Medicine; Linearity; Male; Mass spectrometry; Mathematical analysis; Methods; Methyl alcohol; Middle Aged; Monitoring/Environmental Analysis; Original Paper; Reference Standards; Regression; Sensitivity and Specificity; Silica; Solid Phase Extraction; Spectrometric and optical methods; Stimulants; Pipette tip; Gas chromatography; Dextromethorphan; Mass spectrometry; Solid-phase extraction; Capillary column; Water; Solid phase extraction; Plasma; Electron impact ionization; Impurity; Internal standard; Glycine; Silica; Mixture; Chemical enrichment; Sodium hydroxide; Accuracy; Sample preparation; Detection limit; pH; Silica gel; Monitoring; Variation coefficient; Methanol; Human; Drug; Elution; Sample; Use; Concentration; Method; Pipette; Positive ion; Thickness; Linearity
• ISSN: 1618-2642; 1618-2650; 1618-2650
• DOI: 10.1007/s00216-011-5324-5

Dextromethorphan was extracted from human plasma samples (100 μL) using MonoTip C 18 tips, which are packed with C 18 -bonded monolithic silica gel that is attached to the inside of the tip. The samples, which contained dextromethorphan and trimeprazine as an internal standard (IS), were mixed with 200 μL of distilled water and 50 μL of 1 mol/L glycine–sodium hydroxide buffer (pH 10). The mixture was extracted to the C 18 phase of the tip by 20 sequential aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C 18 phase were then eluted with methanol by five sequential aspirating/dispensing cycles. The eluate was injected directly into a gas chromatograph and detected by a mass spectrometer with selected ion monitoring in positive electron ionization mode. An Equity-5 fused silica capillary column (30 m × 0.32 mm i.d., film thickness 0.5 μm) gave adequate separation of the dextromethorphan, IS, and impurities. The recoveries of dextromethorphan and the IS spiked into plasma were >87.4%. The regression equation for dextromethorphan showed excellent linearity from 2.5 to 320 ng/mL of plasma, and the limit of detection was 1.25 ng/mL of plasma. The intraday and interday coefficients of variation were less than 10.5% and 14.7%, respectively. The accuracy ranged from 91.9% to 107%. The validated method was successfully used to quantify the plasma concentration of dextromethorphan in a human subject after oral administration of the drug.