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    Norman Smith

    King's College London, Biomedical and Health Sciences, Faculty Member
    Papers
    The Anesthesia Database, the Automated Record, and the Quality Assurance Processmore
    by Norman Smith
    Page 1. Page 2.
    Publication Date: 1992
    Publication Name: Int Anesthesiol Clin
    Research Interests:
    Repeatability in column preparation of a reversed-phase C18 monolith and its application to separation of tocopherol homologuesmore
    by Norman Smith
    Publication Date: Jun 15, 2011
    Publication Name: Talanta
    Research Interests:
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    Capillary Liquid Chromatographymore
    by Norman Smith
    Publication Date: May 1, 2004
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    Separation of biomolecules by ¿-high-performance anion-exchange chromatography using a tentacle-like stationary phasemore
    by Norman Smith
    Publication Date: 2005
    Publication Name: Analytical and Bioanalytical Chemistry
    Research Interests:
    Ecstasy Analysis by Monolithic Materials-Capillary Electrochromatographymore
    by Norman Smith
    Monolithic columns were successfully prepared and used with capillary electrochromatography for the analysis of 3,4-methylenedioxymethamphetamine (MDMA) in ecstasy tablets and its metabolites in urine samples. Cationic and neutral... more
    Monolithic columns were successfully prepared and used with capillary electrochromatography for the analysis of 3,4-methylenedioxymethamphetamine (MDMA) in ecstasy tablets and its metabolites in urine samples. Cationic and neutral monolith columns provided better efficiencies than anionic monoliths. The neutral butyl methacrylate (BMA) monolith column provided symmetrical peaks with the highest efficiency, high resolution and short analysis times. The developed method using BMA monolithic column provided the detection limits for MDMA and its metabolites at 1 microg mL(-1) with excellent intra-day and inter-day precision and linearity from 7.5 to 100 microg mL(-1) (R(2) > or = 0.99). MDMA was found as the main component in ecstasy tablets while 4-hydroxy-3-methoxymethamphetamine as the major metabolite in urine samples. High recoveries (97% for MDMA from tablets and 84-102% for its metabolites from urine samples) were obtained using simple ultrasonic extraction for ecstasy tablets and liquid-liquid extraction for urine samples.
    Publication Date: May 1, 2009
    Publication Name: Analytical Sciences
    Research Interests:
    Assessment of Chinese medicinal herb metabolite profiles by UPLC-MS-based methodology for the detection of aristolochic acidsmore
    by Norman Smith
    Publication Date: May 1, 2007
    Publication Name: Journal of Separation Science
    Research Interests:
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    Sub-2µm Particle Packed Column Supercritical Fluid Chromatography Coupled to Mass Spectrometry for Polar Lipid Analysismore
    by Norman Smith
    Publication Date: Nov 1, 2013
    The efficient analysis of neutral and highly polar pharmaceutical compounds using reversed-phase and ion-exchange electrochromatographymore
    by Norman Smith
    ... NW Smith 1. / MB Evans 2 ... At high pH (high elec-troosmotic flow) the test compounds were not eluted from a Spherisorb ODS-1 column, as a result of strong interactions between the analyte and residual silanol groups on the packing... more
    ... NW Smith 1. / MB Evans 2 ... At high pH (high elec-troosmotic flow) the test compounds were not eluted from a Spherisorb ODS-1 column, as a result of strong interactions between the analyte and residual silanol groups on the packing material. ...
    Publication Date: 1995
    Publication Name: Chromatographia
    Research Interests:
    The analysis of pharmaceutical compounds using electrochromatographymore
    by Norman Smith
    Publication Date: 1994
    Publication Name: Chromatographia
    Research Interests:
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    Practical applications of integrated microfluidics for peptide quantificationmore
    by Norman Smith
    Increased pressure to obtain more, higher sensitivity data from less sample is especially critical for large peptides, whose already optimized LC-MS methods are heavily challenged by traditional ligand-binding assays. Critical... more
    Increased pressure to obtain more, higher sensitivity data from less sample is especially critical for large peptides, whose already optimized LC-MS methods are heavily challenged by traditional ligand-binding assays. Critical bioanalytical assays were adapted to integrated microscale LC to reduce sample volumes while increasing sensitivity. Assays for teriparatide, glucagon and human insulin and five analogs were transferred from 2.1 mm analytical scale LC to a 150 µm scale system. This resulted in a 15-30 fold overall improvement in sensitivity derived from increased signal to noise, three to six fold reduction in injection volumes, and a two to five fold reduction in sample consumption. Integrated microscale LC reduces sample consumption while enabling single picomolar quantification for therapeutic and endogenous peptides.
    Publication Date: 2015
    Publication Name: Bioanalysis
    Research Interests:
    Fabrication and evaluation of an organic monolithic column based upon the polymerisation of hexyl methacrylate with 1,6-hexanediol ethoxylate diacrylate for the separation of small molecules by capillary liquid chromatographymore
    by Norman Smith
    This paper describes the fabrication of a new porous monolith, prepared in 100μm i.d. capillaries by the co-polymerisation of hexyl methacrylate with 1,6-hexanediol ethoxylate diacrylate, poly (HMA-co-1,6 HEDA), in the presence of... more
    This paper describes the fabrication of a new porous monolith, prepared in 100μm i.d. capillaries by the co-polymerisation of hexyl methacrylate with 1,6-hexanediol ethoxylate diacrylate, poly (HMA-co-1,6 HEDA), in the presence of azobisisobutyronitrile, 1, 4-butanediol and 1-propanol were used as porogens for the monoliths; the monoliths were then used as a stationary phase for capillary liquid chromatography. Two cross linkers namely 1,6 HEDA and EDMA were utilised in order to investigate the effects of cross linker length on the separation efficiency of small molecules, and it was found that the efficiency of the separation improved tenfold when using the longer cross linker, 1,6 HEDA. This improvement is associated with the increase in number of methylene groups which resulted in an increased number of mesopores, less than 50nm. The 1,6 HEDA based monolith showed a high porosity (90%) and no evidence of swelling or shrinking with the use of organic solvents. Moreover, the 1,6 HEDA monolith demonstrated high reproducibility for the separation of the retained compounds anisole and naphthalene; these showed retention time RSDs of 1.79% and 2.74% respectively. The fabricated monolith also demonstrated high selectivity for neutral non-polar molecules, weak acids, and basic molecules. The asymmetry factors for basic molecules (nortriptyline and amitriptyline) were 1.5 and 1.3 respectively, indicating slight tailing, which is often noticeable on silica based phases due to secondary interactions between basic moieties and the hydroxyl groups of the silica.
    Publication Date: 2015
    Publication Name: Talanta
    Research Interests:
    Organic solvent and temperature-enhanced ion chromatography-high resolution mass spectrometry for the determination of low molecular weight organic and inorganic anionsmore
    by Norman Smith
    There has recently been increased interest in coupling ion chromatography (IC) to high resolution mass spectrometry (HRMS) to enable highly sensitive and selective analysis. Herein, the first comprehensive study focusing on the direct... more
    There has recently been increased interest in coupling ion chromatography (IC) to high resolution mass spectrometry (HRMS) to enable highly sensitive and selective analysis. Herein, the first comprehensive study focusing on the direct coupling of suppressed IC to HRMS without the need for post-suppressor organic solvent modification is presented. Chromatographic selectivity and added HRMS sensitivity offered by organic solvent-modified IC eluents on a modern hyper-crosslinked polymeric anion-exchange resin (IonPac AS18) are shown using isocratic eluents containing 5-50mM hydroxide with 0-80% methanol or acetonitrile for a range of low molecular weight anions (<165Da). Comprehensive experiments on IC thermodynamics over a temperature range between 20-45°C with the eluent containing up to 60% of acetonitrile or methanol revealed markedly different retention behaviour and selectivity for the selected analytes on the same polymer based ion-exchange resin. Optimised sensitivity with H...
    Publication Date: Jan 20, 2015
    Publication Name: Analytica chimica acta
    Research Interests:
    Investigation of microbore UPLC and nontraditional mobile phase compositions for bioanalytical LC-MS/MSmore
    by Norman Smith
    The movement towards environmentally friendly or green chemistry solutions has gained more prominence recently in the scientific community. One way in which scientists can address this issue is to limit the use of hazardous chemicals in... more
    The movement towards environmentally friendly or green chemistry solutions has gained more prominence recently in the scientific community. One way in which scientists can address this issue is to limit the use of hazardous chemicals in their everyday processes. Therefore, the focus of this study was on the utilization of microbore-scale chromatography and nontraditional alcoholic mobile phases as an alternative approach to traditional bioanalytical LC-MS/MS assay parameters. Replacement of the traditional narrowbore LC column with a microbore format reduced solvent consumption and produced a greater than threefold increase in S/N. The nontraditional alcoholic mobile phases, ethanol or isopropanol, produced either greater peak area counts, or S/N, for over half of the compounds evaluated, compared with the traditional organic mobile phases of acetonitrile and methanol. These nontraditional alcoholic mobile phases also showed improved capability in the removal of plasma phospholipid ...
    Publication Date: 2012
    Publication Name: Bioanalysis
    Research Interests:
    Development of a fast method for direct analysis of intact synthetic insulins in human plasma: the large peptide challengemore
    by Norman Smith
    Intact insulins are difficult to analyze by LC-MS/MS due to nonspecific binding and poor sensitivity, solubility and fragmentation. This work aims to provide a simpler, faster LC-MS method and focuses on solving the above issues. A novel... more
    Intact insulins are difficult to analyze by LC-MS/MS due to nonspecific binding and poor sensitivity, solubility and fragmentation. This work aims to provide a simpler, faster LC-MS method and focuses on solving the above issues. A novel charged-surface chromatographic column produced peak widths for insulin that were significantly narrower than traditional C18 columns when using formic acid as mobile phase. Mass spectral fragments m/z >700 provided greater specificity, significantly reducing endogenous background. Detection limits in human plasma were 0.2 ng/ml for insulin glargine, glulisine and detemir, and 0.5 ng/ml for insulin aspart. Average accuracy for standard curve and QC samples was 93.4%. A simple SPE LC-MS analysis was developed for direct, simultaneous quantification of insulin glargine, detemir, aspart and glulisine.
    Publication Date: 2013
    Publication Name: Bioanalysis
    Research Interests:
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    Fabrication of an on-line enzyme micro-reactor coupled to liquid chromatography-tandem mass spectrometry for the digestion of recombinant human erythropoietinmore
    by Norman Smith
    Our aim was to develop a fast and efficient on-line method using micro-reactors for the digestion and deglycosylation of recombinant human erythropoietin extracted from equine plasma. The trypsin digestion micro reactors were fabricated... more
    Our aim was to develop a fast and efficient on-line method using micro-reactors for the digestion and deglycosylation of recombinant human erythropoietin extracted from equine plasma. The trypsin digestion micro reactors were fabricated using fused silica capillaries with either a dextran-modified coating or a porous monolith that was able to immobilise the enzyme. These were both found to be reasonably robust and durable, with the trypsin immobilised on dextran-modified fused silica capillaries offering better reproducibility than the micro-reactor based upon covalent attachment of this enzyme to the polymer. It is also evident that the enzyme attached micro reactors produced some tryptic peptides in a greater yield than in-solution digestion. A peptide-N-glycosidase F reactor was also fabricated and, when coupled with the trypsin reactor, the deaminated peptides T5 DAM and T9 DAM from recombinant human erythropoietin could also be detected by LC-ESI-MS/MS analysis. These results w...
    Publication Date: 2015
    Publication Name: Talanta
    Research Interests:
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    Investigating sub-2 μm particle stationary phase supercritical fluid chromatography coupled to mass spectrometry for chemical profiling of chamomile extractsmore
    by Norman Smith
    Roman and German chamomile are widely used throughout the world. Chamomiles contain a wide variety of active constituents including sesquiterpene lactones. Various extraction techniques were performed on these two types of chamomile. A... more
    Roman and German chamomile are widely used throughout the world. Chamomiles contain a wide variety of active constituents including sesquiterpene lactones. Various extraction techniques were performed on these two types of chamomile. A packed-column supercritical fluid chromatography-mass spectrometry method was designed for the identification of sesquiterpenes and other constituents from chamomile extracts with no derivatization step prior to analysis. Mass spectrometry detection was achieved by using electrospray ionization. All of the compounds of interest were separated within 15 min. The chamomile extracts were analyzed and compared for similarities and distinct differences. Multivariate statistical analysis including principal component analysis and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to differentiate between the chamomile samples. German chamomile samples confirmed the presence of cis- and trans-tonghaosu, chrysosplenols, apigenin digluc...
    Publication Date: Jan 17, 2014
    Publication Name: Analytica chimica acta
    Research Interests:
    Probing gunshot residue, sweat and latent human fingerprints with capillary-scale ion chromatography and suppressed conductivity detectionmore
    by Norman Smith
    Publication Date: 2012
    Publication Name: The Analyst
    Research Interests:
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    Monolithic poly (SPE-co-BVPE) capillary columns as a novel hydrophilic interaction liquid chromatography stationary phase for the separation of polar analytesmore
    by Norman Smith
    A novel hydrophilic interaction liquid chromatography (HILIC) stationary phase was prepared by the co-polymerisation of zwitterionic... more
    A novel hydrophilic interaction liquid chromatography (HILIC) stationary phase was prepared by the co-polymerisation of zwitterionic N,N'-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl) ammonium betaine (SPE) and the crosslinker 1,2-bis(p-vinylphenyl) ethane (BVPE) in the presence of the porogens, toluene and methanol. Monolithic columns were produced by carrying out the α,α'-azoisobutyronitrile (AIBN) initiated reaction for 1, 2, 4, 8 and 12 h inside a 200 μm i.d. fused silica capillary at 75°C (water bath). The optimum polymerisation time was shown to be 2 h, as this resulted in good porosity, due to enlarged flow-channels and the presence of a higher proportion of mesopores provided a relatively larger surface area than the other columns. The chromatographic properties of the optimised poly (SPE-co-BVPE) monolithic column were evaluated with test mixtures containing both basic and neutral compounds in the HILIC gradient separation mode. This produced relatively sharp peaks (average peak width at half height=0.1 min) with average asymmetry factors of 1.4 and baseline resolution was obtained for all the compounds. Using the isocratic separation of the test mixture, the number of theoretical plates (N) per metre calculated was between 26,888 and 35,930 by using average values obtained for triplicate injections of the compounds thiourea, toluene and acrylamide.
    Publication Date: 2012
    Publication Name: Talanta
    Research Interests:
    Systematic evaluation of acetone and acetonitrile for use in hydrophilic interaction liquid chromatography coupled with electrospray ionization mass spectrometry of basic small moleculesmore
    by Norman Smith
    Sub-2-µm particle size hydrophilic interaction liquid chromatography [HILIC] combined with mass spectrometry has been increasing in popularity as a complementary technique to reversed-phase LC for the analysis of polar analytes. The... more
    Sub-2-µm particle size hydrophilic interaction liquid chromatography [HILIC] combined with mass spectrometry has been increasing in popularity as a complementary technique to reversed-phase LC for the analysis of polar analytes. The organic-rich mobile phase associated with HILIC techniques provides increases in compound ionization, due to increased desolvation efficiency during electrospray ionisation mass spectrometric (ESI-MS) analysis. Although recent publications illustrated selectivity and response comparisons between reversed-phase LC/MS and HILIC LC/MS, there are limited discussions evaluating the optimisation of the mass spectrometry parameters regarding analytes and alternative mobile phases. The use of acetone as an alternative organic modifier in HILIC has been investigated with respect to signal-to-noise in ESI-MS for a variety of polar analytes. Analyte reponses were measured based on a variety of cone and capillary voltages at low and high pH in both acetone and acetonitrile. In order to visualise compound behaviour in the ESI source, surface plots were constructed to assist in interpreting the observed results. The use of acetone in ESI is complicated at low m/z due to the formation of condensation products. Favourable responses were observed for certain analytes and we envisage offering an insight into the use of acetone as an alternative to acetonitrile under certain analytical conditions for particular compound classifications for small molecule analysis. We also highlight the importance of optimising source voltages in order to obtain the maximum signal stability and sensitivity, which are invariably, highly solvent composition dependent parameters.
    Publication Date: 2011
    Publication Name: Rapid Communications in Mass Spectrometry
    Research Interests:
    Guidelines for reporting the use of capillary electrophoresis in proteomicsmore
    by Norman Smith
    Publication Date: 2010
    Publication Name: Nature Biotechnology
    Research Interests:
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    Assessment of Chinese medicinal herb metabolite profiles by UPLC-MS-based methodology for the detection of aristolochic acidsmore
    by Norman Smith
    Publication Date: 2007
    Publication Name: Journal of Separation Science
    Research Interests:
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    Mixed-mode reversed-phase and ion-exchange monolithic columns for micro-HPLCmore
    by Norman Smith
    Publication Date: 2008
    Publication Name: Journal of Separation Science
    Research Interests:
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    Highlighting the role of the hydroxyl position on the alkyl spacer of hydroxypropyl-β-cyclodextrin for enantioseparation in capillary electrophoresismore
    by Norman Smith
    Publication Date: 2008
    Publication Name: Journal of Separation Science
    Research Interests:
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    Novel highly hydrophilic zwitterionic monolithic column for hydrophilic interaction chromatographymore
    by Norman Smith
    A novel zwitterionic hydrophilic porous poly(SPV-co-MBA) monolithic column was prepared by thermal co-polymerisation of 1-(3-sulphopropyl)-4-vinylpyridinium-betaine (4-SPV) and... more
    A novel zwitterionic hydrophilic porous poly(SPV-co-MBA) monolithic column was prepared by thermal co-polymerisation of 1-(3-sulphopropyl)-4-vinylpyridinium-betaine (4-SPV) and N,N'-methylenebisacrylamide (MBA). An HILIC/RP dual separation mechanism was observed on this optimised poly(SPV-co-MBA) monolithic column and the composition of the mobile phase corresponding to the transition from the HILIC to the RP mode was around 30% ACN in water. Higher hydrophilicity was achieved on this novel monolithic column compared to the poly(N,N-dimethyl-N-methacryloxyethyl-N-(3-sulphopropyl)ammonium betaine-co-ethylene dimethacrylate) monolithic column. Permeability studies showed slight swelling and/or shrinking with mobile phases of different polarity. As might be anticipated, a weak electrostatic interaction for charged analytes was also observed by studying the influence of mobile phase pH and salt concentration on their retention on the poly(SPV-co-MBA) monolithic column. The final optimised poly(SPV-co-MBA) monolith showed comparable selectivities to commercial ZIC-pHILIC phases for polar test analytes. Fast separation of five pyrimidines and purines was achieved in less than 1 min due to the high permeability of the monolithic column. Additionally, baseline separation of nine benzoic acid derivatives was also observed using either a pH or ACN gradient.
    Publication Date: 2009
    Publication Name: Journal of Separation Science
    Research Interests:
    Determination of trace amount of enantiomeric impurity in therapeutic nicotine derivative using capillary electrophoresis with new imaging technology detectionmore
    by Norman Smith
    Publication Date: 2012
    Publication Name: Journal of Separation Science
    Research Interests:
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    A 150 μm id packed column for the separation of soybean proteins by elution gradient μ-HPLC: Simultaneous separation of soybean proteins from cereal and milk proteinsmore
    by Norman Smith
    ABSTRACT Mu-HPLC has previously been used to increase the resolution and sensitivity of protein separations but never for the analysis of soybean proteins. In this work, soybean proteins were, for the first time, separated using a... more
    ABSTRACT Mu-HPLC has previously been used to increase the resolution and sensitivity of protein separations but never for the analysis of soybean proteins. In this work, soybean proteins were, for the first time, separated using a capillary column with an internal diameter of 150 microm packed with a Genesis C18 stationary phase (4 microm, 300 angstroms) and UV detection. TFA and acetic acid were investigated as ion-pairing reagents in order to optimise water-ACN gradients to achieve this separation. The column showed good selectivity enabling the separation of soybean proteins from other vegetable proteins such as cereal (wheat, rice and corn) and also from milk proteins. The developed method was applied to the detection of soybean proteins in commercial products elaborated with mixtures of vegetable proteins.
    Publication Date: 2006
    Publication Name: Journal of Separation Science
    Research Interests:
    Preparation and characterization of long alkyl chain methacrylate-based monolithic column for capillary chromatographymore
    by Norman Smith
    Publication Date: 2007
    Publication Name: Journal of Biochemical and Biophysical Methods
    Research Interests:
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    Prediction of Variability in CYP3A4 Induction Using a Combined 1 H NMR Metabonomics and Targeted UPLC–MS Approachmore
    by Norman Smith
    The activity of Cytochrome P450 3A4 (CYP3A4) enzyme is associated with many adverse or poor therapeutic responses to drugs. We used (1)H NMR-based metabonomics to identify a metabolic signature associated with variation in induced CYP3A4... more
    The activity of Cytochrome P450 3A4 (CYP3A4) enzyme is associated with many adverse or poor therapeutic responses to drugs. We used (1)H NMR-based metabonomics to identify a metabolic signature associated with variation in induced CYP3A4 activity. A total of 301 female twins, aged 45--84, participated in this study. Each volunteer was administered a potent inducer of CYP3A4 (St. John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate (300 mg). Pre- and postintervention fasting urine samples were used to obtain metabolite profiles, using (1)H NMR spectroscopy, and were analyzed using UPLC--MS to obtain a marker for CYP3A4 induction, via the ratio of 3-hydroxyquinine to quinine (3OH-Q:Q). Multiple linear regression was used to build a predictive model for 3OH-Q:Q values based on the preintervention metabolite profiles. A combination of seven metabolites and seven covariates showed a strong (r = 0.62) relationship with log(3OH-Q:Q). This regression model demonstrated significant (p < 0.00001) predictive ability when applied to an independent validation set. Our results highlight the promise of metabonomics for predicting CYP3A4-mediated drug response.
    Publication Date: 2011
    Publication Name: Journal of Proteome Research
    Research Interests:
    Comprehensive investigation of the influence of acidic, basic, and organic mobile phase compositions on bioanalytical assay sensitivity in positive ESI mode LC/MS/MSmore
    by Norman Smith
    Publication Date: 2012
    Publication Name: Journal of Pharmaceutical and Biomedical Analysis
    Research Interests:
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    Rapid quantification of quinine and its major metabolite (3S)-3-hydroxyquinine in diluted urine by UPLC–MS/MSmore
    by Norman Smith
    Publication Date: 2011
    Publication Name: Journal of Pharmaceutical and Biomedical Analysis
    Research Interests:
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    Direct injection of human serum and pharmaceutical formulations for glucosamine determination by CE-C4D methodmore
    by Norman Smith
    A simple CE-C(4)D method has been developed for the determination of glucosamine by direct injection of human serum and pharmaceutical samples. Glucosamine was electrokinetically injected and analysed in its protonated form using 20mM... more
    A simple CE-C(4)D method has been developed for the determination of glucosamine by direct injection of human serum and pharmaceutical samples. Glucosamine was electrokinetically injected and analysed in its protonated form using 20mM MES/His (pH 6) as background electrolyte in order to separate it from the matrix and to provide a better response to the C(4)D detector. Separation of glucosamine in human serum and pharmaceutical samples was performed in 3 min without the need for protein precipitation or matrix removal. Good precision in terms of %RSD for the migration time and peak area were less than 1.91% (n = 10). The conductivity signal was linear with glucosamine concentration in the range 0.10-2.50mg/mL, with a detection limit of 0.03 mg/mL. Recoveries of glucosamine in serum and pharmaceutical samples were 86.5-104.78%. The method was successfully applied for the determination of the glucosamine content in pharmaceutical formulations and validated with high performance liquid chromatography (HPLC). Good agreements were observed between the developed method, label values and the HPLC method. Glucosamine could be detected in spiked serum sample by direct injection. This was not possible by HPLC due to co-eluting interferences.
    Publication Date: 2011
    Publication Name: Journal of Chromatography B
    Research Interests:
    High sensitivity LC–MS/MS method for direct quantification of human parathyroid 1–34 (teriparatide) in human plasmamore
    by Norman Smith
    Teriparatide, the 1-34 fragment of human parathyroid hormone, is used to treat osteoporosis patients with a high risk of fracture by stimulating new bone formation. Routinely teriparatide is quantified using radioimmunoassay however the... more
    Teriparatide, the 1-34 fragment of human parathyroid hormone, is used to treat osteoporosis patients with a high risk of fracture by stimulating new bone formation. Routinely teriparatide is quantified using radioimmunoassay however the LC-MS/MS described here has the potential to achieve greater accuracy and precision, higher specificity, and is readily implemented in routine bioanalytical laboratories. Hence a complete method combining effective sample prep with appropriate LC separation and selected reaction monitoring (SRM) MS detection was developed to selectively separate teriparatide from closely related endogenous peptides and to reduce interferences. Samples were concentrated without evaporation, minimizing the risk of adsorptive losses. Chromatography was performed on a sub 2μm particle charged surface hybrid column, which provided significantly higher peak capacity than a traditional C18 column when formic acid was used as the mobile phase modifier. Total LC cycle time was 6min. An LOD of 15pg/mL (3.6fmol/mL) from 200μL of human plasma was readily achieved and standard curves were accurate and precise from 15pg/mL to 500pg/mL. Mean QC accuracies ranged from 90% to 106%. Mean QC precision was better than 7%. The CV of matrix factors across 6 sources of human plasma was 5%. The assay presented here is the first LC-MS method which reaches clinically relevant detection limits for teriparatide.
    Publication Date: 2013
    Publication Name: Journal of Chromatography B
    Research Interests:
    Ultra High Resolution SFC - MS as a High Throughput Platform for Metabolic Phenotyping: Application to Metabolic Profiling of Rat and Dog Bilemore
    by Norman Smith
    Publication Date: 2014
    Publication Name: Journal of Chromatography B
    Research Interests:
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    Comparison of styrene–divinylbenzene-based monoliths and Vydac nano-liquid chromatography columns for protein analysismore
    by Norman Smith
    Publication Date: 2004
    Publication Name: Journal of Chromatography A
    Research Interests:
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    Developments in the use and fabrication of organic monolithic phases for use with high-performance liquid chromatography and capillary electrochromatographymore
    by Norman Smith
    Publication Date: 2008
    Publication Name: Journal of Chromatography A
    Research Interests:
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    Enantiomeric separations by capillary electrochromatography using a macrocyclic antibiotic chiral stationary phasemore
    by Norman Smith
    Publication Date: 1999
    Publication Name: Journal of Chromatography A
    Research Interests:
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    Characterisation of electroosmotic flow in capillary electrochromatography columnsmore
    by Norman Smith
    Currently available capillary electrochromatography (CEC) instrumentation using UV-Vis detection dictates the use of duplex columns. Due to discontinuities (electric field strength and conductivity) that arise at the boundary between the... more
    Currently available capillary electrochromatography (CEC) instrumentation using UV-Vis detection dictates the use of duplex columns. Due to discontinuities (electric field strength and conductivity) that arise at the boundary between the packed and open sections in these columns, the determination of the electroosmotic flow (EOF) is complicated. Thiourea has been found to be an accurate EOF marker under the conditions employed in this study. By injecting this compound onto a fully packed column and comparing the obtained mobilities with those calculated from measured zeta potential values a value for tortuosity has been obtained. The use of laser Doppler velocimetry (LDV) for the measurement of zeta potential has been found to be the most direct and rapid method of characterising silica support materials in terms of electroosmotic mobility. The open section in duplex CEC columns has been shown to influence the actual column flow-rate. The EOF measured using duplex columns of varying packed and open section lengths have been compared with those obtained for a fully packed column.
    Publication Date: 2001
    Publication Name: Journal of Chromatography A
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    Novel zwitterionic polyphosphorylcholine monolithic column for hydrophilic interaction chromatographymore
    by Norman Smith
    Publication Date: 2009
    Publication Name: Journal of Chromatography A
    Research Interests:
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    Preparation and application of hydrophilic monolithic columnsmore
    by Norman Smith
    Publication Date: 2011
    Publication Name: Journal of Chromatography A
    Research Interests:
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    A simple high pH liquid chromatography–tandem mass spectrometry method for basic compounds: Application to ephedrines in doping control analysismore
    by Norman Smith
    Publication Date: 2011
    Publication Name: Journal of Chromatography A
    Research Interests:
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    Comparison of aqueous and non-aqueous capillary electrochromatography for the separation of basic solutesmore
    by Norman Smith
    The analysis of basic compounds by capillary electrochromatography (CEC) on silica-based materials using conventional HPLC stationary phases has failed to address the problem of severe peak tailing and non-reproducible chromatography.... more
    The analysis of basic compounds by capillary electrochromatography (CEC) on silica-based materials using conventional HPLC stationary phases has failed to address the problem of severe peak tailing and non-reproducible chromatography. Several new generation stationary phases were evaluated using aqueous and non-aqueous mobile phases. The best results were obtained in the aqueous mode using Waters Symmetry Shield RP-8, a material in which the residual silanol groups were shielded by an octylcarbamate function. For comparison, experiments were carried out using unmodified silica.
    Publication Date: 2000
    Publication Name: Journal of Chromatography A
    Research Interests:
    Comparison of the electroosmotic flow profiles and selectivity of stationary phases used in capillary electrochromatographymore
    by Norman Smith
    ... that in CEC, stationary phase particle size does not influence the electroosmotic flow (EOF) through ... possible to use very small particles and still maintain a good flow through the ... If no pH adjustment was necessary, mobile... more
    ... that in CEC, stationary phase particle size does not influence the electroosmotic flow (EOF) through ... possible to use very small particles and still maintain a good flow through the ... If no pH adjustment was necessary, mobile phases were prepared simply by mixing the appropriate ...
    Publication Date: 1999
    Publication Name: Journal of Chromatography A
    Research Interests:
    Highlighting the possible secondary interactions in the role of balhimycin and its analogues for enantiorecognition in capillary electrophoresismore
    by Norman Smith
    Publication Date: 2010
    Publication Name: Journal of Chromatography A
    Research Interests:
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    UV gradient combined with principal component analysis: Highly sensitive and specific high performance liquid chromatography analysis of cosmetic creamsmore
    by Norman Smith
    HPLC has been employed to develop a method for the analysis of cosmetic creams, in particular the compounds hydroquinone, phenol and six preservatives have been studied. UV tuning was optimized as a gradient to achieve lower limits of... more
    HPLC has been employed to develop a method for the analysis of cosmetic creams, in particular the compounds hydroquinone, phenol and six preservatives have been studied. UV tuning was optimized as a gradient to achieve lower limits of detection compared to those of a previously validated method. In addition the chromatograms were then exported, aligned and visualized in a principal component analysis (PCA) model. The results were the highly efficient separation of the eight studied compounds. All the compounds showed good linear correlation coefficients (≥ 0.9997), the detection limit was found to be in the range of 15-200 ng/mL, a 10-fold improvement for the preservatives on previous methodology and the average recovery was within limits between 83% and 117% with a relative standard deviation (RSD) less than 3.6% (n=6). The PCA plot was constructed from the UV optimized cosmetic samples chromatograms from real samples, real samples that were spiked and quality controls. Quality controls contained the eight compounds and showed complete clustering in the PCA and three spiked samples containing six to seven toxic components clustered in the same quadrant. The method is highly sensitive and its potential use as a method that could be employed in the control of cosmetics, particularly those containing banned or suspected toxic additives, has been demonstrated.
    Publication Date: 2012
    Publication Name: Journal of Chromatography A
    Research Interests:
    Comparison of reversed-phase and hydrophilic interaction liquid chromatography for the separation of ephedrinesmore
    by Norman Smith
    Publication Date: 2012
    Publication Name: Journal of Chromatography A
    Research Interests:
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    Addressing the challenge of limited sample volumes in in vitro studies with capillary-scale microfluidic LC-MS/MSmore
    by Norman Smith
    Miniaturization of chromatographic separation systems provides a means of greatly increasing sensitivity in LC-MS. In this article, we demonstrate the use of an integrated microfluidic chromatographic device for the LC-MS/MS investigation... more
    Miniaturization of chromatographic separation systems provides a means of greatly increasing sensitivity in LC-MS. In this article, we demonstrate the use of an integrated microfluidic chromatographic device for the LC-MS/MS investigation of the in vitro microsomal metabolism of the model drug propranolol using a sample volume of 1 µl of a 1-µM incubation. With such samples the system was capable of obtaining high-quality MS and MS/MS data from the injection of test drug substance containing sufficient information to correctly derive the structure of the drug metabolites. The analytical column was tolerant to the injection of a large percentage of organic solvent in the sample and still delivered a high-quality separation. The data suggest that these types of micro-LC-MS/MS devices are robust enough for routine applications and well suited to the analysis of small samples. Other potential applications include the generation of pharmacokinetic profiles from the reduced sample volumes...
    Publisher: ncbi.nlm.nih.gov
    Publication Date: 2011
    Publication Name: Bioanalysis
    Research Interests:
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    Detection of anionic energetic material residues in enhanced fingermarks on porous and non-porous surfaces using ion chromatographymore
    by Norman Smith
    The ability to link criminal activity and identity using validated analytical approaches can be of great value to forensic scientists. Herein, the factors affecting the recovery and detection of inorganic and organic energetic material... more
    The ability to link criminal activity and identity using validated analytical approaches can be of great value to forensic scientists. Herein, the factors affecting the recovery and detection of inorganic and organic energetic material residues within chemically or physically enhanced fingermarks on paper and glass substrates are presented using micro-bore anion exchange chromatography with suppressed conductivity detection. Fingermarks on both surfaces were enhanced using aluminium powder or ninhydrin after spiking with model test mixtures or through contact with black-powder substitutes. A quantitative study of the effects of environmental/method interferences, the sweat matrix, the surface and the enhancement technique on the relative anion recovery of forensically relevant species is presented. It is shown that the analytical method could detect target analytes at the nanogram level even within excesses of enhancement reagents and their reaction products when using solid phase extraction and/or microfiltration. To our knowledge, this work demonstrates for the first time that ion chromatography can detect anions in energetic materials within fingermarks on two very different surfaces, after operational enhancement techniques commonly used by forensic scientists and police have been applied.
    Publication Date: 2013
    Publication Name: Forensic Science International
    Research Interests:
    Characterisation of gunshot residue from three ammunition types using suppressed anion exchange chromatographymore
    by Norman Smith
    Publication Date: 2012
    Publication Name: Forensic Science International
    Research Interests:
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    Monolithic and packed particle materials for in-line pre-concentration in capillary electrophoresis for 4-hydroxy-3-methoxy-methamphetamine and terbutalinemore
    by Norman Smith
    Publication Date: 2008
    Publication Name: ELECTROPHORESIS
    Research Interests:
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    Highlighting the role of the chlorine substituents in the glycopeptide antibiotic balhimycin for chiral recognition in capillary electrophoresismore
    by Marcelo Bertazzo and Norman Smith
    Publication Date: 2006
    Publication Name: ELECTROPHORESIS
    Research Interests:
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