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A novel miniaturized, solid-contact potentiometric screen-printed electrode was developed for highly sensitive and selective determination of lidocaine anesthetic. The electrode integrated single-walled carbon nanotubes as a solid-contact material and a molecularly imprinted polymer as a recognition sensory material. The performance characteristics of the electrode were evaluated and optimized to display a Nernstian slope of 58.92 ± 0.98 mV/decade over a linear concentration range of 4.53 × 10−7 to 6.18 × 10−3 mol/l within < 6 s. The detection limit was 7.75 × 10−8 mol/l (18.16 ng/ml) of lidocaine. The use of the molecularly imprinted polymer significantly enhanced the selectivity of the electrode, and carbon nanotubes increased the sensitivity, accuracy, and potential stability. The electrode was successfully used for determining lidocaine in pharmaceutical preparations and human urine. The results favorably compared with data obtained by liquid chromatography–tandem mass spectrometry. [ABSTRACT FROM AUTHOR]

In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl–carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02–5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0–108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5–7.7% and 1.5–8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma. [ABSTRACT FROM AUTHOR]

In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl–carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02–5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0–108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5–7.7% and 1.5–8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.

The demand for clinical toxicology analytical methods for identifying drugs of abuse and medicinal drugs is steadily increasing. Structural elucidation of amino amide‐type local anesthetic drugs and their main metabolites by GC‐EI‐MS and LC‐ESI‐MS/MS is of great analytical challenge. These compounds exhibit only/mostly fragments/product ions representing the amine‐containing residue, while the aromatic amide moiety remains unidentified. This task becomes even more complicated when discrimination between positional isomers of such compounds is required. Here, we report the development of a derivatization procedure for the differentiation and structural elucidation of a mixture of local anesthetic drugs and their metabolites that possess tertiary and secondary amines in water and urine. A method based on two sequential “in‐vial” instantaneous derivatization processes at ambient temperature followed by LC‐ESI‐MS/MS analysis was developed. 2,2,2‐Trichloro‐1,1‐dimethylethyl chloroformate (TCDMECF) was utilized to selectively convert the secondary amines into their carbamate derivatives, followed by hydrogen peroxide addition to produce the corresponding tertiary amine oxides. The resulting derivatives exhibited rich fragmentation patterns, enabling improved structural elucidation of the original compounds. The developed method was successfully applied to the differentiation and structural elucidation of prilocaine and its four positional isomers, which all possess similar GC and LC retention times and four of them exhibit almost identical EI‐MS and ESI‐MS/MS spectra, enabling their structural elucidation in a single LC‐ESI‐MS/MS analysis. The developed technique is fast and simple and enables discrimination between isomers based on different diagnostic ions/fragmentation patterns. [ABSTRACT FROM AUTHOR]

A novel PRiME (process, robustness, improvements, matrix effects, ease of use) pass-through cleanup procedure has been developed to improve the existing commercially available designs. Carbon nanosorbents, i.e., magnetic modified carboxyl-graphene (Mag-CG) and magnetic modified carboxyl-carbon nanotubes (Mag-CCNTs), have been synthesised and evaluated in PRiME pass-through cleanup procedure for human plasma prior to analysis of 10 selected local anesthetic drugs by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). The matrix effect, an interesting phenomenon of ion suppression for local anesthetic drugs containing ester group and ion enhancement for other drugs containing acylamino group, has been minimized using carbon nanosorbents PRiME pass-through cleanup procedure. Under the optimal conditions, the obtained results show higher cleanup efficiency of the carbon nanosorbents with recoveries between 70.2% and 126%. Furthermore, the carbon nanosorbents are also evaluated for reuse up to 80–100 times. The limits of quantification (LOQs) for local anesthetic drugs are in the range of 0.024–0.15 μg/L. Validation results on linearity, specificity, accuracy, and precision, as well as the application to the analysis of lidocaine in five patients recruited from the lung cancer demonstrate the applicability to clinical studies. [ABSTRACT FROM AUTHOR]

The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Na v s), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Na v s. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Na v s in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs. [ABSTRACT FROM AUTHOR]

ABSTRACT 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 n m, respectively. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A model peptide that their sequence corresponds to the linker part between domain III and IV of rat brain type IIA Na+ channel has been synthesized for the conformational affect study corresponded to different gated states of Na+ channel. Nuclear magnetic resonance spectra of local anesthetic (LA) diphenyl drugs, such as phenytoin, in presence of a model peptide in both phosphate buffer and phospholipid bicelles (dimyristotl phosphocholine/dihexanoyl phospholcholine), which micelles serve to mimic the peptide–lipid interactions, have been measured to obtain information of the interactions between selected drugs and model peptide. Molecular modeling is performed to help to provide possible conformational information about the polypeptide LIII–IV that may be critical for recognition and signal transduction of inactivated Na+ channel. The voltage-sensing mechanism of Na+ channel involves the movement of the inactivation particles (Ile, Phe, and Met) in the LIII–IV while binding to S4–S5 intracellular region within DIII and DIV. The movement of LIII–IV making its C-terminal residues, including Glu1492 and Glu1493, may aligned near and stabilize the LAs bound with their receptors. [ABSTRACT FROM AUTHOR]

Enantiomeric separation of alkoxysubstituted esters of phenylcarbamic acid (local anesthetic drugs) is carried out using high performance liquid chromatography (HPLC) with two chiral stationary phases. The teicoplanin chiral stationary phase—chirobiotic T and the teicoplanin chiral stationary phase without the pendant carbohydrate moieties—chirobiotic teicoplanin aglycone (TAG) were used. The influence of the sugar units, the concentration of the ionic modifiers (diethylamine), the influence of the position and of number of carbon atoms in the analytic alkoxychain substituent, and the composition of the mobile phase; on retention factors and resolution of enantiomers were investigated. By comparison of chromatographic parameters obtained by using both chiral stationary phases, the influence of carbohydrate moieties on the mechanism of chiral separation could be evaluated. The interaction mechanism of the enantiomeric separations is discussed. Better separation, in terms of—greater values of Rij of enantiomers—was achieved with the chirobiotic TAG column. [ABSTRACT FROM AUTHOR]

Ranolazine is a new antianginal drug approved for clinical use in the United States in January 2006. A study published in this same issue of the British Journal of Pharmacology characterizes ranolazine block of late sodium current caused by the long QT syndrome 3 mutations. This commentary discusses the implications of that study and the background and implications for block of late cardiac sodium current in general. [ABSTRACT FROM AUTHOR]

• NTM-COFs was prepared and used in matrix effect-free on-line pass-through cleanup procedure. • LC-MS/MS method was developed for the fast detection of local anesthetic in plasma samples. • The cleanup and analysis procedures are carried out simultaneously. • The developed method can be applied to the clinical studies. A novel nano-titania modified covalent organic frameworks (NTM-COFs) has been synthesized and characterized by transmission electron microscopy (TEM) and scanning electron micrographs (SEM). Besides, NTM-COFs, as efficient sorbent, has also been evaluated in the on-line pass-through cleanup procedure prior to the analysis of local anesthetic drugs (lidocaine, bupivacaine and tetracaine) in human plasma by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). Under optimum conditions, the level of matrix effects can be dramatically reduced by the NTM-COFs based on-line pass-through cleanup procedure, with acceptable recoveries ranging from 88.8% to 103%. Satisfactory trueness and precision of the proposed method were also obtained, with the within- and between-run RSDs less than 7.0% and relative error (REs) less than 12%. The limits of detections (LODs) of lidocaine, bupivacaine and tetracaine were 0.029 μg·L−1, 0.027 μg·L−1 and 0.016 μg·L−1, respectively. The analytical method has been successfully applied for the determination of the plasma concentrations of bupivacaine in five parturients who received an epidural administration of bupivacaine hydrochloride during vaginal delivery. Results demonstrate the applicability of the developed NTM-COFs on-line pass-through cleanup procedure coupled with LC-MS/MS method to clinical studies. [ABSTRACT FROM AUTHOR]

The pore domain of human voltage-dependent cardiac sodium channel Na v 1.5 (hNa v 1.5) is the crucial binding targets for anti-arrhythmics drugs and some local anesthetic drugs but its three-dimensional structure is still lacking. This has affected the detailed studies of the binding features and mechanism of these drugs. In this paper, we present a structural model for open-state pore domain of hNa v 1.5 built using single template ROSETTA-membrane homology modeling with the crystal structure of Na v Ms. The assembled structural models are evaluated by rosettaMP energy and locations of binding sites. The modeled structures of the pore domain of hNa v 1.5 in open state will be helpful to explore molecular mechanism of a state-dependent drug binding and help designing new drugs.