Determination of metoprolol enantiomers in human plasma and saliva samples utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

A sensitive, accurate and reliable bioanalytical method for the enantioselective determination of metoprolol in plasma and saliva samples utilizing liquid chromatography-electrospray ionization tandem mass spectrometry was developed and validated. Human plasma and saliva samples were pretreated by microextraction by packed sorbent (MEPS) prior to analysis. A new MEPS syringe form with two inputs was used. Metoprolol enantiomers and internal standard pentycaine (IS) were eluted from MEPS sorbent using isopropanol after removal of matrix interferences using aliquots of 5% methanol in water. Complete separation of metoprolol enantiomers was achieved on a Cellulose-SB column (150 × 4.6 mm, 5 µm) using isocratic elution with mobile phase 0.1% ammonium hydroxide in hexane-isopropanol (80:20, v/v) with a flow rate of 0.8 mL/min. A post-column solvent-assisted ionization was applied to enhance metoprolol ionization signal in positive mode monitoring (+ES) using 0.5% formic acid in isopropanol at a flow rate of 0.2 mL/min. The total chromatographic run time was 10 min for each injection. The detection of metoprolol in plasma and saliva samples was performed using triple quadrupole tandem mass spectrometer in +ES under the following mass transitions: m/z 268.08 → 72.09 for metoprolol and m/z 303.3 → 154.3 for IS. The linearity range was 2.5-500 ng/mL for both R- and S-metoprolol in plasma and saliva. The limits of detection and quantitation for both enantiomers were 0.5 and 2.5 ng/mL respectively, in both matrices (plasma and saliva). The intra- and inter-day precisions were presented in terms of RSD values for replicate analysis of quality control samples and were <5%; the accuracy of determinations varied from 96 to 99%. The method was able to determine the therapeutic levels of metoprolol enantiomers in both human plasma and saliva samples successfully, which can aid in therapeutic drug monitoring in clinical laboratories. Copyright © 2016 John Wiley & Sons, Ltd.

Microextraction by packed sorbent: an emerging, selective and high-throughput extraction technique in bioanalysis.

Sample preparation is an important analytical step regarding the isolation and concentration of desired components from complex matrices and greatly influences their reliable and accurate analysis and data quality. It is the most labor-intensive and error-prone process in analytical methodology and, therefore, may influence the analytical performance of the target analytes quantification. Many conventional sample preparation methods are relatively complicated, involving time-consuming procedures and requiring large volumes of organic solvents. Recent trends in sample preparation include miniaturization, automation, high-throughput performance, on-line coupling with analytical instruments and low-cost operation through extremely low volume or no solvent consumption. Micro-extraction techniques, such as micro-extraction by packed sorbent (MEPS), have these advantages over the traditional techniques. This paper gives an overview of MEPS technique, including the role of sample preparation in bioanalysis, the MEPS description namely MEPS formats (on- and off-line), sorbents, experimental and protocols, factors that affect the MEPS performance, and the major advantages and limitations of MEPS compared with other sample preparation techniques. We also summarize MEPS recent applications in bioanalysis.

Molecularly imprinted polymer in microextraction by packed sorbent for the simultaneous determination of local anesthetics: lidocaine, ropivacaine, mepivacaine and bupivacaine in plasma and urine samples.

This study presents the use of molecularly imprinted polymer (MIP) as packing material for microextraction by packed syringe (MEPS) to achieve higher extraction selectivity. Pentycaine was used as template for MIP. Development and validation of the determination of lidocaine, ropivacaine, mepivacaine and bupivacaine in human plasma and urine samples utilizing MIP-MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. The MEPS MIP-cartridge could be used for 100 extractions before it was discarded. The extraction recovery ranged from 60 to 80%. The correlation coefficients values were >0.999 for all assays using lidocaine, ropivacaine, mepivacaine and bupivacaine in the calibration range 5-2000 nmol/L. The accuracy of the studied compounds, given as a percentage variation from the nominal concentration values, ranged from -4.9 to 8.4% using plasma and urine samples. The between-batch precision, given as the relative standard deviation, at three different concentrations (quality control samples) was ranged from -4.7 to 14.0% and from 1.8 to 12.7% in plasma and urine, respectively. The lower limit of quantification and limit of detection of the studied substances were 5.0 and 1.0 nm, respectively.

Effects of thermal degradation products from polyurethane foams based on toluene diisocyanate and diphenylmethane diisocyanate on isolated, perfused lung of guinea pig.

OBJECTIVES: The composition of thermal degradation products from two types of polyurethane foams, one based on toluene diisocyanate (TDI) and the other on diphenylmethane diisocyanate (MDI), was analyzed and their toxic lung effects were compared. METHODS: Isolated perfused lungs of guinea pig were subjected to thermal decomposition products of polyurethane foams from an aerosol generator with compartments for diluting, mixing, and sampling. RESULTS: Thermal degradation of MDI-based polyurethane foams released MDI, phenyl isocyanate, and methyl isocyanate. The emitted particulate fraction was 75% for MDI, whereas that for TDI from TDI-based polyurethane foam was 3%. Thermal degradation products from MDI-based foam caused a pronounced dose-dependent decrease in the measured lung function parameters (conductance and compliance). In contrast, the thermal degradation products from TDI-based foam did not cause any decrease in lung function. CONCLUSIONS: Thermal degradation products generated from MDI-based polyurethane foam were more toxic to the lung than those generated from TDI-based polyurethane foam. This difference was probable due to MDI in the particle phase.

A needle extraction utilizing a molecularly imprinted-sol-gel xerogel for on-line microextraction of the lung cancer biomarker bilirubin from plasma and urine samples.

In the present work, a needle trap utilizing a molecularly imprinted sol-gel xerogel was prepared for the on-line microextraction of bilirubin from plasma and urine samples. Each prepared needle could be used for approximately one hundred extractions before it was discarded. Imprinted and non-imprinted sol-gel xerogel were applied for the extraction of bilirubin from plasma and urine samples. The produced molecularly imprinted sol-gel xerogel polymer showed high binding capacity and fast adsorption/desorption kinetics for bilirubin in plasma and urine samples. The adsorption capacity of molecularly imprinted sol-gel xerogel polymer was approximately 60% higher than that of non-imprinted polymer. The effect of the conditioning, washing and elution solvents, pH, extraction time, adsorption capacity and imprinting factor were investigated. The limit of detection and the lower limit of quantification were set to 1.6 and 5nmolL(-1), respectively using plasma or urine samples. The standard calibration curves were obtained within the concentration range of 5-1000nmolL(-1) in both plasma and urine samples. The coefficients of determination values (R(2)) were ≥0.998 for all runs. The extraction recovery was approximately 80% for BR in the human plasma and urine samples.

Evaluation of solid-phase microextraction with PDMS for air sampling of gaseous organophosphate flame-retardants and plasticizers.

As an inexpensive, simple, and low-solvent consuming extraction technique, the suitability of solid-phase microextraction (SPME) with polydimethylsiloxane (PDMS) sorbent was investigated as a quantitative method for sampling gaseous organophosphate triesters in air. These compounds have become ubiquitous in indoor air, because of their widespread use as additive flame retardants/plasticizers in various indoor materials. Results obtained by sampling these compounds at controlled air concentrations using SPME and active sampling on glass fibre filters were compared to evaluate the method. A constant linear airflow of 10 cm s(-1) over the fibres was applied to increase the extraction rate. For extraction of triethyl phosphate with a 100-microm PDMS fibre, equilibrium was achieved after 8 h. The limit of detection was determined to be less than 10 pg m(-3). The PDMS-air partition coefficients, Kfs, for the individual organophosphate triesters were determined to be in the range 5-60 x 10(6) at room temperature (22-23 degrees C). Air measurements were performed utilising the determined coefficients for quantification. In samples taken from a lecture room four different airborne organophosphate esters were identified, the most abundant of which was tris(chloropropyl) phosphate, at the comparatively high level of 1.1 microg m(-3). The results from SPME and active sampling had comparable repeatability (RSD less than 17%), and the determined concentrations were also similar. The results suggest that the investigated compounds were almost entirely associated with the gaseous phase at the time and place sampled.