title: On-line solid phase extraction using the Prospekt-2 coupled with a liquid chromatography/tandem mass spectrometer for the determination of dextromethorphan, dextrorphan and guaifenesin in human plasma.
abstract: An on-line liquid chromatography/tandem mass spectrometry (LC-MS/MS) procedure, using the Prospekt- 2 system, was developed and used for the determination of the levels of the active ingredients of cough/cold medications in human plasma matrix. The experimental configuration allows direct plasma injection by performing on- line solid phase extraction (SPE) on small cartridge columns prior to elution of the analyte(s) onto the analytical column and subsequent MS/MS detection. The quantitative analysis of three analytes with differing polarities, dextromethorphan (DEX), dextrorphan (DET) and guaifenesin (GG) in human plasma presented a significant challenge. Using stable-isotope-labeled internal standards for each analyte, the Prospekt-2 on-line methodology was evaluated for sensitivity, suppression, accuracy, precision, linearity, analyst time, analysis time, cost, carryover and ease of use. The lower limit of quantitation for the on-line SPE procedure for DEX, DET and GG was 0.05, 0.05 and 5.0 ng mL(-1), respectively, using a 0.1 mL sample volume. The linear range for DEX and DET was 0.05-50 ng mL(-1) and was 5-5,000 ng mL(-1) for GG. Accuracy and precision data for five different levels of QC samples were collected over three separate days. Accuracy ranged from 90% to 112% for all three analytes, while the precision, as measured by the %RSD, ranged from 1.5% to 16.0%
authors.affiliation: Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd, Mason, OH 45040-8006, USA.
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Kuhlenbeck
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Eichold
authors.forename: Steven H
authors.initials: SH
authors.lastname: Hoke
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Baker
authors.forename: Robert
authors.initials: R
authors.lastname: Mensen
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Wehmeyer
mesh_terms: D000996:Antitussive Agents / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003915:Dextromethorphan / Q000097:blood*; D003917:Dextrorphan / Q000097:blood*; D005100:Expectorants / Q000032:analysis*; D006140:Guaifenesin / Q000032:analysis*; D006801:Humans; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*
chemical_list: D000996:Antitussive Agents; D005100:Expectorants; D003917:Dextrorphan; D006140:Guaifenesin; D003915:Dextromethorphan