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Biomedical subjects

I S Lurie

Publications and source records attributed to I S Lurie.

At least 19 recordsLinked to original sources

Profiling of impurities in heroin by capillary electrochromatography and laser-induced fluorescence detection.

Capillary electrochromatography (CEC) with laser-induced fluorescence (LIF) detection was investigated for the analysis of acidic and neutral impurities in heroin. The phenanthrene-like heroin impurities exhibit high native fluorescence when excited with a doubled argon ion laser (operating at 257 nm). The limit of detection for acetylthebaol is 66 pg ml(-1). CEC-LIF analysis of heroin samples of different geographical origin gave distinguishable peak-enriched chromatograms. A sulfonic acid C12 polymer monolith column provided similar resolving power to a 1.5 mm non-porous ODS column for the isocratic analysis of a refined heroin sample. Analysis of a crude heroin sample via a multi-step gradient CEC resolved a significantly higher number of peaks than gradient high-performance liquid chromatography or micellar electrokinetic capillary chromatography.

Chromatography, Micellar Electrokinetic Capillary↗

Advances ofcapillary electrophoresis in clinical and forensic analysis (1999-2000).

In this paper, capillary electrophoresis in clinical and forensic analysis is reviewed on the basis of the literature of 1999, 2000 and the first papers in 2001. An overview of progress relevant examples for each major field of application, namely (i) analysis of drug seizures, explosives residues, gunshot residues and inks, (ii) monitoring of drugs, endogenous small molecules and ions in biofluids and tissues, (iii) general screening for serum proteins and analysis of specific proteins (carbohydrate deficient transferrin, alpha1-antitrypsin, lipoproteins and hemoglobins) in biological fluids, and (iv) analysis of nucleic acids and oligonucleotides in biological samples, including oligonucleotide therapeutics, are presented.

Clinical Chemistry Tests↗

Use of dynamically coated capillaries for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine using capillary electrophoresis.

A rapid, accurate, precise, reproducible, economical, and environmentally gentle method using capillary electrophoresis (CE) is presented for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine in seized drugs. The methodology uses a 32 cm by 50 microm capillary (length to detector 23.5 cm) with a commercially available buffer kit and diode array UV detection. Dynamic coating of the capillary surface is accomplished by flushing with base for 1 min, a proprietary polycation for 1 min, and then a proprietary polyanion for 2 min. This approach provides a relatively high and stable electroosmotic flow (EOF), even at low pHs. The background electrolyte (BGE) contains 75 mM phosphate buffer (pH 2.5) with the same polyanion as above. Using this methodology, amphetamine, methamphetamine, MDA, MDMA, MDEA, and an internal standard (n-butylamphetamine) are baseline resolved in less than 5 min. The run-to-run migration time %RSDs and peak area %RSDs are typically <0.3% and <2.1%, respectively. The day-to-day and capillary-to-capillary migration time %RSDs are <1.5% and <2.1%, respectively. The %RSDs of the relative migration times compared with the internal standard on a day-to-day and capillary-to-capillary basis are <0.2% and <0.06%, respectively. The linear dynamic range using peak areas range from 0.003 to 0.10 mg/mL. The correlation coefficients are >0.9998, with all calibration curves passing at or near the origin. Similar data are obtained for cocaine and its internal standard henyltoloxamine. None of the compounds usually encountered in illicit samples interfere with the target compound (e.g., methamphetamine and cocaine) or the internal standard. Quantitative results for synthetic mixtures and seized exhibits are in good agreement with actual values, and also with results obtained from other techniques. The relatively high EOF for the dynamically coated capillary system allows for the screening of basic, acidic, and neutral adulterants in drug seizures; identification is facilitated by the use of automated UV library searches.

Journal Article↗

Profiling of impurities in illicit methamphetamine by high-performance liquid chromatography and capillary electrochromatography.

High performance liquid chromatography (HPLC) with photodiode array (PDA) UV and fluorescence (FL) detection, and capillary electrochromatography (CEC) with laser-induced fluorescence (LIF) detection were investigated for the analysis of acidic extracts derived from illicit methamphetamine. These compounds include major impurities from the hydriodic acid/red phosphorous reduction method, i.e., 1,3-dimethyl-2-phenylnaphthalene and 1-benzyl-3-methylnaphthalene, and other trace-level, structurally related impurities. For certain of these solutes, HPLC with conventional FL detection gave at least a 60x increase in sensitivity over UV detection. In addition, other highly fluorescent impurities were detected in methamphetamine produced via four other synthetic routes. The use of a rapid scanning FL detector (with acquisition of "on the fly" excitation or emission) provided structural information and gave "optimum" excitation and emission detection wavelengths. CEC with LIF detection using UV laser excitation provided greatly improved chromatography over HPLC, with good detection limits in the low ng/ml range. Both methodologies provide good run-to-run repeatability, and have the capability to distinguish between samples.

Chromatography, High Pressure Liquid↗

On-chip chiral and achiral separation of amphetamine and related compounds labeled with 4-fluoro-7-nitrobenzofurazane.

Amphetamine and analogous compounds have been labeled with 4-fluoro-7-nitrobenzofurazane and analyzed on a microfabricated chip. Separation of norephedrine, ephedrine, cathinone, pseudoephedrine, methcathinone, amphetamine and methamphetamine is demonstrated using micellar electrokinetic capillary chromatography (MEKC) and laser-induced fluorescence (LIF) detection. Chiral separations of individual drugs were studied using neutral and negatively charged cyclodextrins (CDs) with and without the addition of an organic modifier and/or sodium dodecyl sulfate (SDS). The best results were obtained using a highly sulfated gamma-CD (HS-gamm-CD) in combination with a low concentration of SDS. To obtain complete separation of a mixture of (+/-)-norephedrine, (+/-)ephedrine, (+/-)-pseudoephedrine, (+/-)-methcathinone, (+/-)-amphetamine and (+/-)-methamphetamine it was necessary to add a small amount (1.5 mM) of SDS to the separation buffer. Optimized chiral separation was achieved within 7 min using an S-folded separation channel, a separation voltage of 8 kV and a buffer consisting of 50 mM phosphate (pH 7.35), 10 mM HS-gamma-CD and 1.5 mM SDS.

4-Chloro-7-nitrobenzofurazan↗

Capillary electrophoresis in clinical and forensic analysis: recent advances and breakthrough to routine applications.

This paper is a comprehensive review article on capillary electrophoresis (CE) in clinical and forensic analysis. It is based upon the literature of 1997 and 1998, presents CE examples in major fields of application, and provides an overview of the key achievements encountered, including those associated with the analysis of drugs, serum proteins, hemoglobin variants, and nucleic acids. For CE in clinical and forensic analysis, the past two years witnessed a breakthrough to routine applications. As most coauthors of this review are associated with diagnostic or forensic laboratories now using CE on a routine basis, this review also contains data from routine applications in drug, protein, and DNA analysis. With the first-hand experience of providing analytical service under stringent quality control conditions, aspects of quality assurance, assay specifications for clinical and forensic CE and the pros and cons of this maturing, cost-and pollution-controlled age technology are also discussed.

Electrophoresis, Capillary↗

Capillary electrochromatography of cannabinoids.

The applicability of capillary electrochromatography (CEC) with photodiode array UV detection for the analysis of cannabinoids is presented. Baseline separation of seven cannabinoids (cannabigerol, cannabidiol, cannabinol, delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, cannabichromene, delta-9-tetrahydrocannabinolic acid) is obtained using a 3-micron CEC Hypersil C18 capillary with an acetonitrile/phosphate (pH 2.57) mobile phase. The effects of acetonitrile concentration, buffer concentration, voltage, temperature, stationary phase, and column length on the separation of the cannabinoids were investigated. Good short- and long-term precision in retention times are observed, with significant improvement obtained using relative retention times with cannabinol as reference compound. Although short- and long-term peak area precisions are poor, satisfactory reproducibility is obtained using relative peak areas with cannabinol as reference compound. The applicability of the CEC methodology to drug seizures was demonstrated on marijuana and hashish. Using a high-sensitivity UV flow cell with an extended path length of 1.2 mm, concentration sensitivities approaching HPLC were obtained.

Acetonitriles↗

Capillary electrophoresis analysis of isomeric truxillines and other high molecular weight impurities in illicit cocaine.

The analysis of by-products and impurities in illicit cocaine, including the isomeric truxillines, is important for derivation of both strategic and tactical intelligence. In the present study, various capillary electrophoresis techniques were investigated for this purpose. The use of the anionic beta-cyclodextrin sulfobutyl ether IV as a run buffer additive at pH 8.6 gave a good separation of the truxillines and similar high molecular weight impurities in less than eight minutes. These impurities were first isolated from the bulk cocaine matrix using liquid-liquid extraction and size-exclusion high performance liquid chromatography. There was a red shift in the UV spectra obtained for the truxillines using photodiode array (PDA) UV detection during CE analysis. This anomalous behavior is attributed to photo-degradation of the truxillines during the PDA-UV irradiation process. Laser-induced fluorescence detection using a UV krypton/fluoride laser provided greater selectivity and sensitivity versus UV detection for certain uncharacterized high molecular weight impurities.

Cocaine↗

Effects of various anionic chiral selectors on the capillary electrophoresis separation of chiral phenethylamines and achiral neutral impurities present in illicit methamphetamine.

In this study, various anionic chiral selectors were investigated for the capillary electrophoresis (CE) separation of six chiral phenethylamines and three achiral neutral impurities which are commonly identified in illicit methamphetamine. Analyses were carried out at pH 8 (high osmotic flow) with untreated capillaries using 25 mM chiral surfactant or 10 mM charged cyclodextrin. The chiral selectors included the micelle (R)-N-dodecoxycarbonylvaline (EnantioSelect (R)-Val-1) (ES) and the cyclodextrins sulfobutyl(IV)-ether-beta-cyclodextrin (SBE(IV)-beta-CD) (BSB4), SBE(VII)-beta-CD (BSB7), SBE(XII)-beta-CD (BSB 12), SBE(IV)-gamma-CD (GSB-4), SBE(VII)-gamma-CD (GSB-7), sulfated(XI)-alpha-cyclodextrin (SU(XI)-alpha-CD (AS11), SU(VII)-beta-CD (BS7), SU(XII)-beta-CD (BS12) and SU(XIII)-beta-CD (GS13). Enantiomeric and achiral selectivity strongly depends on the size of the CD, the average degree of substitution, and the type of substitution. ES exhibits good performance for the neutral solutes, but exhibits enantiomeric selectivity only for the alpha-hydroxyphenethylamines. GS13 provides the best overall enantiomeric selectivity. All fifteen solutes related to methamphetamine are simultaneously separated using BSB7.

Anions↗

Application of micellar electrokinetic capillary chromatography to the analysis of illicit drug seizures.

The application of micellar electrokinetic capillary chromatography (MECC) to the analysis of illicit drug seizures is presented. Areas investigated include general screening and qualitative and, in some instances, quantitative analysis of various drugs, including heroin, opium, cocaine, amphetamines, LSD and anabolic steroids. Due to its high efficiency, high selectivity and general applicability, MECC is well suited for forensic drug analyses.

Amphetamines↗

Separation and detection of acidic and neutral impurities in illicit heroin via capillary electrophoresis.

The separation and detection of acidic and neutral impurities in illicit heroin using capillary electrophoresis (CE) is described. Separations were achieved using charged cyclodextrin modified micellar electrokinetic capillary chromatography. The use of the anionic beta-cyclodextrin sulfobutyl ether 1V in combination with sodium dodecyl sulfate significantly increased resolution. Improved selectivity and/or sensitivity in detection was obtained using photodiode array ultraviolet and laser-induced fluorescence detection. The phenanthrene-like heroin impurities exhibit high native fluorescence under krypton-fluoride laser excitation (248 nm). The limit of detection by laser-induced fluorescence detection for one of these solutes (acetylthebaol) is 1.8 ng/ml, 500 times more sensitive than UV. This methodology is applicable to analysis of both crude and refined heroin.

Drug Contamination↗

Analysis of heroin drug seizures by Micellar Electrokinetic Capillary Chromatography (MECC).

A rapid procedure using Micellar Electrokinetic Capillary Chromatography (MECC) is presented for the quantitation of illicit heroin samples. This analytical system resolves heroin from accompanying impurities and adulterants enabling accurate quantitation via the use of an internal standard. An aqueous run buffer consisting of 40 mmol sodium dodecyl sulfate, 8.5 mmol sodium phosphate, 8.5 mmol sodium borate and 15% acetonitrile is used with a 27 cm x 50 microns fused silica capillary column. Linearity, accuracy and reproducibility studies of heroin using this method are established. Comparisons to a commonly used gas chromatographic method show excellent correlation. Due to its high resolution and speed, this MECC system also serves as a screening procedure to detect impurities and adulterants present in heroin samples. Relative migration times of various opiates and adulterants are reported. With minor exceptions, complete separation of numerous compounds is achieved within five minutes, including compounds that are difficult to analyze by gas chromatography such as morphine, O6-acetylmorphine, aspirin and salicylic acid.

Chromatography, Gas↗

Chiral resolution of cationic drugs of forensic interest by capillary electrophoresis with mixtures of neutral and anionic cyclodextrins.

Chiral resolution of a number of cationic drugs of forensic interest (amphetamine, methamphetamine, cathinone, methcathinone, cathine, cocaine, propoxyphene, and various alpha-hydroxyphenethylamines) is achieved via capillary electrophoresis (CE) with added cyclodextrins (CDs), including novel mixtures of neutral and anionic CDs. In the latter studies, resolution and migration speed are readily adjusted by varying the ratio of the two added CDs, as the anionic CD acts as a counter-migrating complexing reagent. The neutral CD, heptakis(2,6-di-O-methyl)-beta-CD, was found suitable for the analysis of illicit cocaine and khat leaves (Catha edulis Forsk), which contain (-)-alpha-aminopropiophenone ((-)-cathinone), (+)-norpseudoephedrine (cathine), (-)-norephedrine, and trace levels of the phenylpentenylamines (+)-merucathinone, (+)-merucathine, and possibly (-)-pseudomerucathine. The use of mixtures of the neutral and the anionic CD (beta-CD sulfobutyl ether IV) was found suitable for the analysis of illicit amphetamine, methamphetamine, methcathinone, and propoxyphene. A model is presented for the impact of mixtures of neutral and anionic CDs on migration behavior and chiral resolution in CE.

Cyclodextrins↗

The determination of anabolic steroids by MECC, gradient HPLC, and capillary GC.

Methodologies are presented for the qualitative and quantitative determinations of anabolic steroids in forensic exhibits using micellar electrokinetic capillary chromatography (MECC), high performance liquid chromatography (HPLC) and capillary gas chromatography (GC). Analyses of representative pharmaceutical dosage forms (including a commercial aqueous suspension, a commercial tablet, several commercial oil samples and various simulated dosage units) were performed using a simple, one step quantitative extraction procedure with methanol. Good agreement was obtained between all three techniques. Retention, migration and linearity data are presented and compared for over twenty anabolic steroids commonly encountered in forensic exhibits. A principal component analysis study confirmed the orthogonality of the three techniques.

Anabolic Agents↗

Capillary gas chromatographic-electron capture detection of coca-leaf-related impurities in illicit cocaine: 2,4-diphenylcyclobutane-1,3-dicarboxylic acids, 1,4-diphenylcyclobutane-2,3-dicarboxylic acids and their alkaloidal precursors, the truxillines.

A method has been developed that allows for the detection of the eleven stereoisomers of diphenylcyclobutanedicarboxylic acid in illicit cocaine samples, including alpha-, gamma-, and epsilon-truxillic acids and beta- and delta-truxinic acids. These, and other carboxylic acids, were also detected as ester moieties of alkaloidal impurities in illicit cocaine as well as in alkaloids of the South American coca leaf, e.g., alpha- and beta-truxilline. After lithium aluminum hydride reduction of the acidic and basic extracts of a prepared sample, the reduced species were derivatized with heptafluorobutyric anhydride in the presence of pyridine. The heptafluorobutyryl derivatives of the reduced diphenylcyclobutanedicarboxylic compounds were easily detected on-column at low picogram levels using a moderately polar fused-silica capillary column in the splitless mode and interfaced with a 63Ni electron-capture detector.

Alcohols↗

Analysis of manufacturing by-products and impurities in illicit cocaine via high-performance liquid chromatography and photodiode array detection.

An high-performance liquid chromatography (HPLC) method is reported for the detection of manufacturing by-products and impurities in illicitly produced cocaine. For the first time peak enriched chromatograms were obtained using HPLC, and were accomplished using reversed-phase chromatography and photodiode array detection. The use of sodium dodecylsulfate as an ion-pairing reagent permitted the simultaneous separation of acids, mono-protic amines and di-protic amines, and, in combination with gradient elution, greatly increased the number of compounds separated. A mixed binary-ternary gradient was used to further optimize the separation. Dual UV detection at 215 and 277 nm was used. The chromatogram at 215 nm consisted first of carboxylic acids such as benzoic acid, cinnamic acid (cis and trans) and several isomers of truxillic and truxinic acid; next the mono-protic amines benzoylecgonine and cinnamoylcocaine (cis and trans); and last a group of compounds which are believed to be isomers of the di-protic amine truxilline. In addition, simultaneous detection at 277 nm permitted the selective detection of various compounds, some of which are additional components. The rapid acquisition of UV spectra greatly facilitated compound identification.

Chromatography, High Pressure Liquid↗

An improved method for the rapid screening of illicit cocaine preparations using high performance liquid chromatography with electrochemical detection.

Electrochemical detection in HPLC offers a very sensitive and selective alternative to UV detection for a number of classes of compounds. While there have been no reports of the use of electrochemical detection for the determination of cocaine in illicit preparations or biological fluids, it is now possible to use on-line, continuous post-column photolytic derivatization to generate electroactive species from cocaine which may then be detected downstream using a conventional electrochemical detector operated at oxidative working electrode potentials. In this manuscript the construction, optimization and characterization of system parameters are discussed, and the sensitive and highly selective nature of this novel detection method is demonstrated to be uniquely suited to the rapid identification and quantitation of cocaine in simulated illicit preparations.

Chromatography, High Pressure Liquid↗

Photolytic derivatization for improved LCEC determinations of pharmaceuticals in biological fluids.

Although electrochemical (EC) methods have been demonstrated to be sensitive and selective, wide use of EC detection in high performance liquid chromatographic (HPLC) assays in forensic and clinical toxicology laboratories has not been forthcoming. This fact is due to the general difficulty involved with the use of reductive EC detection methods, as well as to the lack of EC response in either the oxidative or reductive mode, for a number of classes of drugs having substantial clinical and forensic importance. The use of an on-line, post-column, continuous photolytic derivatization step, followed by conventional oxidative amperometric detection, alleviates many of these problems. In this report, the use of HPLC-photolysis-EC (HPLC-h nu-EC) for the trace determination of a number of controlled substances in biological fluids is presented. Following system optimization, the determination of phenobarbital, cocaine, methylphenidate, and several 1,4-benzodiazepines (and metabolites) is linear over three orders of magnitude. In addition, HPLC-h nu-EC offers a sensitive approach for these compounds, in that limits of detection (LODs) are all below 1 microgram/ml, ranging from 1 ng/ml to 750 ng/ml. The validity of this newer method is demonstrated in collaborative studies involving the trace determinations of phenobarbital in human serum, and chlordiazepoxide and its major metabolite, norchlordiazepoxide, in human urine. Finally, the authors' view of the role of HPLC-h nu-EC in the clinical and forensic toxicology laboratory is presented.

Anti-Anxiety Agents↗