Dextromethorphan In Plasma Research Articles

Analysis of dextromethorphan and pseudoephedrine in human plasma and urine samples using hollow fiber-based liquid–liquid–liquid microextraction and corona discharge ion mobility spectrometry

We report on the use of hollow fiber liquid-liquid-liquid microextraction (HF-LLLME) followed by corona discharge ion mobility spectrometry for the determination of dextromethorphan and pseudoephedrine in urine and plasma samples. The effects of pH of the donor phase, stirring rate, ionic strength and extraction time on HF-LLLME were optimized. Under the optimized conditions, the linear range of the calibration curves for dextromethorphan in plasma and urine, respectively, are from 1.5 to 150 and from 1 to 100 ng mL−1. The ranges for pseudoephedrine, in turn, are from 30 to 300 and from 20 to 200 ng mL−1. Correlation coefficients are better than 0.9903. The limits of detection are 0.6 and 0.3 ng mL−1 for dextromethorphan, and 8.6 and 4.2 ng mL−1 for pseudoephedrine in plasma and urine samples, respectively. The relative standard deviations range from 6 to 8%.

Rapid bioanalytical determination of dextromethorphan in canine plasma by dilute-and-shoot preparation combined with one minute per sample LC-MS/MS analysis to optimize formulations for drug delivery

The determination of dextromethorphan in canine plasma is used to demonstrate the high throughput bioanalytical approach of automated dilute-and-shoot (DAS) sample preparation followed by a 1 min isocratic liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Dilute-and-shoot preparation is commonly used for the determination of drugs in several biological matrices such as urine and saliva, but is not typically used with plasma samples because the amount of protein present in plasma can lead to a variety of problems including column failure. As a result, plasma sample preparation usually removes protein by precipitation, extraction or filtration; however, the dilute-and-shoot approach solubilizes proteins throughout the chromatographic portion of the assay. The attributes of this approach are compared with a previously validated liquid/liquid extraction procedure for determination of dextromethorphan in plasma. Accuracy and precision of both methods are similar. The lower limit of quantitation (LLOQ) of the dilute-and-shoot approach is much higher at 2 ng/ml versus 5 pg/ml with the liquid/liquid extraction; however, the sample throughput of the preparation portion of the dilute-and-shoot approach is more than 50-fold greater. The ruggedness of the dilute-and-shoot method was thoroughly investigated because of the problems traditionally associated with the direct injection of diluted plasma onto an LC-MS/MS instrument. With the optimal conditions, greater than 1000 injections of diluted plasma have been successfully performed on a single column in less than 19 h making this technique an excellent approach for the rapid preparation and high throughput of plasma samples containing drug levels in the ng/ml range or higher. Application of this methodology to measure the levels of dextromethorphan in canine plasma to evaluate drug delivery from various formulations is also presented.

Highly sensitive high-performance liquid chromatographic-tandem mass spectrometric method for the analysis of dextromethorphan in human plasma

A stable-isotope-dilution HPLC-tandem mass spectrometry-based method was developed for the determination of dextromethorphan in human plasma. Plasma samples were prepared for analysis by solid-phase extraction on octadecylsilane extraction cartridges. Dextromethorphan and the deuterium-labeled dextromethorphan internal standard were chromatographed on a short reversed-phase column and detected by a selected-reaction-monitoring scheme. Linear standard curves were obtained over three orders of magnitude and the limit of quantitation for dextromethorphan was 50 pg/ml, using a 1-ml plasma sample. The combination of HPLC and electrospray tandem mass spectrometry resulted in a rapid, selective and sensitive method for the analysis of dextromethorphan in plasma. The method was applied for the evaluation of the pharmacokinetic profile of dextromethorphan in human volunteers following peroral administration.

Applicability of continuous-flow atom borbardment liquid chromatography—mass spectrometry in bionalysis : Dextromethorphan in plasma

Continuous-flow fast atom bombardment (CF-FAB) is an interface for combined liquid chromatography—mass spectrometry using FAB as the ionization method. The applicability of CF-FAB for quantitative bionalysis was studied for a model compound, dextromethorphan, in plasma samples using conventionla high-performance liquid chromatography. The flow-rate reduction was achieved either by splitting or by the phase-system switching approach. The features of both systems are discussed.

Phenotypic differences in dextromethorphan metabolism.

Polymorphic differences in dextromethorphan metabolism were observed in three studies conducted in a total of 44 subjects (of Dutch origin) administered 60 mg dextromethorphan hydrobromide as an OROS tablet. Mean plasma dextromethorphan (DM) concentrations after a single dose and at steady state were 4-75 times higher in the poor metabolizers (PM) relative to the extensive metabolizers (EM). Following a single dose, the mean areas under the plasma concentration-time curve (AUC, 0-24 hr) of DM, total dextrorphan (DR), and total 3-hydroxymorphinan (HM) were 6.9-fold higher, 17.4-fold lower, and 11-fold lower, respectively, for the PM than for the EM. Correspondingly, steady-state AUC values were 52.8 times higher, 6.7 times lower, and 3.3 times lower for DM, total DR, and total HM, respectively, for the PM relative to the EM. Drug/metabolite ratios (DMR) for amounts excreted in the urine of DR and HM indicated polymorphism in O-demethylation of DM since DMR for PM was 352 and 338 times higher than that for EM for DR and HM, respectively. However, polymorphism in N-demethylation was not observed. Ratios of conjugated/free dextrorphan and 3-hydroxymorphinan excreted in the urine suggest also a lack of conjugative capacity in the PM, relative to the EM. The overall incidence of PM was 9.1% in this population.

Determination of Dextromethorphan in Biological Fluids by Liquid Chromatography by Using Semi-microbore Columns

A sensitive, specific procedure for the determirjation of dextromethorphan in plasma and urine in dogs is described. The use of a semi-microbore column, 2.1 mm i.d. × 25 cm resulted in a detection limit of 1 ng/mL in plasma and 25 ng/mL in urine. PJasma (3 mL) is extracted in CCl4 and the drug is back-extracted with 3% acetic acid. The chromatographic separation is carried out using a 5-μm particle size octadecyl-bonded column, and the drug is monitored by a fluorescence detector. The results after 10-mg oral administrations of dextromethorphan to dogs are provided.