Simultaneous determination of dextromethorphan, dextrorphan, and guaifenesin in human plasma using semi-automated liquid/liquid extraction and gradient liquid chromatography tandem mass spectrometry
| Autor: | Steven H. Hoke, Thomas H. Eichhold, David L. McCauley-Myers, Gary A. Thompson, Deepa Ashok Khambe |
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| Rok vydání: | 2007 |
| Předmět: |
Guaifenesin
Analyte Accuracy and precision Chemistry Pharmaceutical Drug Storage Clinical Biochemistry Analytical chemistry Administration Oral Pharmaceutical Science Guidelines as Topic Tandem mass spectrometry Dextromethorphan Analytical Chemistry Double-Blind Method Drug Stability Reference Values Tandem Mass Spectrometry Liquid chromatography–mass spectrometry Liquid–liquid extraction Dextrorphan Drug Discovery medicine Humans Chromatography High Pressure Liquid Spectroscopy Expectorants Autoanalysis Cross-Over Studies Chromatography Chemistry Extraction (chemistry) Reproducibility of Results Reference Standards Antitussive Agents Drug Combinations Linear Models medicine.drug |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 43:586-600 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2006.07.018 |
| Popis: | A method for the simultaneous determination of dextromethorphan (DEX), dextrorphan (DET), and guaifenesin (GG) in human plasma was developed, validated, and applied to determine plasma concentrations of these compounds in samples from six clinical pharmacokinetic (PK) studies. Semi-automated liquid handling systems were used to perform the majority of the sample manipulation including liquid/liquid extraction (LLE) of the analytes from human plasma. Stable-isotope-labeled analogues were utilized as internal standards (ISTDs) for each analyte to facilitate accurate and precise quantification. Extracts were analyzed using gradient liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Use of semi-automated LLE with LC-MS/MS proved to be a very rugged and reliable approach for analysis of more than 6200 clinical study samples. The lower limit of quantification was validated at 0.010, 0.010, and 1.0 ng/mL of plasma for DEX, DET, and GG, respectively. Accuracy and precision of quality control (QC) samples for all three analytes met FDA Guidance criteria of +/-15% for average QC accuracy with coefficients of variation less than 15%. Data from the thorough evaluation of the method during development, validation, and application are presented to characterize selectivity, linearity, over-range sample analysis, accuracy, precision, autosampler carry-over, ruggedness, extraction efficiency, ionization suppression, and stability. Pharmacokinetic data are also provided to illustrate improvements in systemic drug and metabolite concentration-time profiles that were achieved by formulation optimization. |
| Databáze: | OpenAIRE |
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