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Debbie L. Kuhlenbeck,a Thomas H. Eichhold,b Steven H. Hoke,
II,b Timothy R. Baker,a Robert Mensenc and Kenneth R. Wehmeyera,*
aProcter & Gamble
Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd, Mason, OH 45040-8006, USA. E-mail: wehmeyer.kr@pg.com
bThe Procter &
Gamble Company, Health Care Research Center, 8700 Mason-Montgomery Rd, Mason, OH 45040-8006, USA
cSpark Holland Inc., 666 Plainsboro Rd,
Plainsboro, NJ 08536, USA |
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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 0.05Ő50 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% |
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Keywords:
dextromethorphan, dextrorphan, guaifenesin,
Prospekt-2, LC-MS/MS, on-line SPE |
