Apply Of LC/MS/MS Method In The Pharmacokinetic Study Of Multi-component Anti-cold Drugs

The basis of all pharmacokinetic evaluations is reliable assays to quantify the trace drugs and/or metabolites in biological matrices using modern sensitive instrumental analytical techniques. Being both specific and universal, LC/MS has now become a valuable technique in the analyst's toolbox. The LC/MS often proved to be superior with respect to sensitivity, selectivity and speed of analysis, compared with other analytical methods, and was widely used for the multi-components determinations. Two rapid, sensitive and specific methods for quantitative analyses of trace multi-components in plasma were developed and validated by liquid chromatography/tandem mass spectrometry in this thesis. The methods have been successfully applied to pharmacokinetic studies.1. Simultaneous determination of methylephedrine and noscapine in human plasma by liquid chromatography/tandem mass spectrometryA specific and sensitive method has been developed and validated for simultaneous quantification of methylephedrine and noscapine in human plasma. The analytes were extracted from plasma samples by liquid-liquid extraction, separated through a Diamonsil C₁₈ column and detected by tandem mass spectrometer with an atmospheric pressure chemical ionization interface. Diphenhydramine was used as the internal standard. Selected reaction monitoring (SRM) using the precursor→product ion combination of m/z 180→m/z 162, m/z 414→m/z 220 and m/z 256→m/z 167 was used to quantify methylephedrine, noscapine and the internal standard, respectively. The linear calibration curves were obtained in the concentration range of 0.1-100 ng/mL for both methylephedrine and noscapine. The method has a lower limit of quantification (LLOQ) of 0.1 ng/ml for methylephedrine and noscapine, respectively. The intra- and inter-run precisions, expressed as the relative standard deviation (RSD), were less than 5.2% for methylephedrine and 6.7% for noscapine, The inter-day relative error as determined from quality control samples was less than 3.0% for each analyte. The assay was successfully employed in a pharmacokinetic study after an oral administration of a multicomponent formulation containing 20 mg dl-methylephedrine hydrochloride, 16 mg noscapine, 300 mg paracetamol and 1 mg of chlorpheniramine maleate.2. Simultaneous determination of pseudoephedrine and dextromethorphan in human plasma by liquid chromatography-tandem mass spectrometry methodA rapid, sensitive and highly selective liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of pseudoephedrine and dextromethorphan. The analytes were extracted from plasma samples by liquid-liquid extraction, separated on a Zorbax SB-C₈ column and detected by tandem mass spectrometry with a electrospray ionization interface. Diphenhydramine was used as the internal standard. The method has a lower limit of quantification (LLOQ) of 0.5 ng/ml and 0.05ng/ml for pseudoephedrine and dextromeorphan, respectively. The chromatographic run time was approximately 3.5 min. The standard calibration curves were linear in the concentration ranges of 0.50 ng/ml-400 ng/ml for pseudoephedrine and 0.05-40.0 ng/ml for dextromethorphan in human plasma. The intra- and inter-run precisions, expressed as the relative standard deviation (RSD), were less than 13.8% and 11.5%, determined from QC samples for pseudoephedrine and dextromethorphan, and accuracy was within±1.7% and±1.7% in terms of relative error, respectively. The method was successfully applied for the evaluation of the pharmacokinetics of pseudoephedrine and dextromethorphan in 20 volunteers after an oral dose of 60 mg pseudoephedrine hydrochloride, 30 mg dextromethorphan hydrobromide, 500 mg paracetamol and 200 mg of Guaifenesin.