Comparison of different mass spectrometry techniques in the measurement of L‐[ring‐13C6]phenylalanine incorporation into mixed muscle proteins

Precise measurement of low enrichment of stable isotope labeled amino‐acid tracers in tissue samples is a prerequisite in measuring tissue protein synthesis rates. The challenge of this analysis is augmented when small sample size is a critical factor. Muscle samples from human participants following an 8 h intravenous infusion of L‐[ring‐¹³C₆]phenylalanine and a bolus dose of L‐[ring‐¹³C₆]phenylalanine in a mouse were utilized. Liquid chromatography tandem mass spectrometry (LC/MS/MS), gas chromatography (GC) MS/MS and GC/MS were compared to the GC‐combustion‐isotope ratio MS (GC/C/IRMS), to measure mixed muscle protein enrichment of [ring‐¹³C₆]phenylalanine enrichment. The sample isotope enrichment ranged from 0.0091 to 0.1312 molar percent excess. As compared with GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS showed coefficients of determination of R² = 0.9962 and R² = 0.9942, and 0.9217 respectively. However, the precision of measurements (coefficients of variation) for intra‐assay are 13.0%, 1.7%, 6.3% and 13.5% and for inter‐assay are 9.2%, 3.2%, 10.2% and 25% for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. The muscle sample sizes required to obtain these results were 8 µg, 0.8 µg, 3 µg and 3 µg for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. We conclude that LC/MS/MS is optimally suited for precise measurements of L‐[ring‐¹³C₆]phenylalanine tracer enrichment in low abundance and in small quantity samples. Copyright © 2013 John Wiley & Sons, Ltd.     

Electrochemical and Spectroscopic Studies on the Interaction of Gallocyanine with DNA

The interaction of gallocyanine (GC) with double‐stranded DNA (dsDNA) in pH 3.5 Tris‐HCl buffer solution was investigated by electrochemical methods and spectrophotometric methods as well. In the potential scan range of ‐0.25 ? +0.18 V(vs. SCE), GC had a couple of well‐defined redox peaks at ‐0.022 V and ‐0.069 V on a cyclic voltammogram at the scan rate of 100.0 mV/s, respectively. After the addition of dsDNA into the GC solution, the redox‐peak currents decreased obviously and the peak potentials shifted positively. The results demonstrated that GC binding to DNA was caused by intercalation. Electrochemical parameters such as the electron number (n), the charge transfer coefficient (α) and the electrochemical reaction standard rate constant (k_s) were calculated and compared in the absence and presence of dsDNA. Almost unchanged values of the electrochemical parameters after adding dsDNA showed that non‐electroactive complexes were formed when GC interacted with DNA. The results indicated that the decrease of the redox‐peak currents was caused by the decrease of the free concentration of GC in the reaction solution. The binding constant and binding ratio were investigated by spectrophotometric methods. DNA concentration can be determined by the decrease of the peak current of GC. The linear range for dsDNA was in the range of 1.45 × 10^?7 ? 1.45 × 10^?6mol/Land 1.45 × 10^?6 ? 1.45 × 10^?5 mol/L, respectively with the linear regression equation as Δi_P (10^?7 A) = 0.037 + 0.018C (10^?7mol/L), and Δi_P (10^?7 A) = 0.25 + 0.041C (10^?6mol/L), respectively, and the detection limit (3σ) was 1.13 × 10^?7 mol/L.     

High temperature (GC)2 and (GC)2/CI-MS of nucleosides: Analysis of purinyl nucleoside isomer composition

The analysis of low-volatile polar nucleosides by (GC)²/FID and (GC)²/CI-MS, employing HMDS-deactivated glass capillary columns and on-column injection, is described. The four linkage isomers of a specific nucleoside, formed in the synthetic procedure, are in each case sufficiently well separated in the chromatogram; GC/CI-MS allows for a differentiation of N-7 and N-9 linkage isomers.     

Nafion-multi-walled Carbon Nanotubes Supported Tris(bipyridyl)iron(II) for Nicotine Detection

This work reports an electrochemical sensing framework for nicotine determination based on glassy carbon electrode (GC) immobilized with Fe(bpy)₃²⁺ (where bpy is 2,2’-bipyridyl) supported by Nafion and multi-walled carbon nanotubes (Nf-MWCNTs). Fe(bpy)₃²⁺ immobilized Nf-MWCNTs modified GC (GC/Nf-MWCNTs/Fe(bpy)₃²⁺) manifests stable redox peaks, characteristics of Fe(bpy)₃²⁺. The GC/Nf-MWCNTs/Fe(bpy)₃²⁺ exhibits effective electrochemical oxidation of nicotine, diminishing the overpotential relative to GC/Nf-MWCNTs. The limit of detection is 0.1 μM (experimentally observed) with two different linear calibration ranges between 0.1 to 600 μM and 600 to 3000 μM. Electrocatalytic responses observed at GC/Nf-MWCNTs/Fe(bpy)₃²⁺ indicate superior performance for nicotine determination with acceptable selectivity, stability, and reproducibility. Additionally, the nicotine present in real samples such as beedi and tobacco are also analyzed with satisfactory recovery percentages.     

Tyrosine sensing on phthalic anhydride functionalized chitosan and carbon nanotube film coated glassy carbon electrode

Phthaloylchitosan (PHCS) has been synthesized by a simple and low-cost method using chitosan and phthalic anhydride as organic precursors by microwave irradiation. Techniques of nuclear magnetic resonance (NMR), FT-IR spectroscopy and transmission electron microscope (TEM) were used to characterize the structure and properties of the Phthaloylchitosan. Moreover, glassy carbon electrode modified with Phthaloylchitosan and carbon nanotube (PHCS–CNT/GCE) was prepared by casting of the PHCS–CNT solution on GCE. The electrochemical behavior of PHCS–CNT/GCE was investigated and compared with the electrochemical behavior of Phthaloylchitosan modified GC (PHCS/GC), carbon nanotube modified GC (CNT/GC) and unmodified GC using cyclic voltammetry (CV). The Phthaloylchitosan film is electrochemically inactive; similar background charging currents are observed at bare GC. Electrochemical parameters, including apparent diffusion coefficient for the Fe(CN)₆^3-/4- redox probe at PHCS–CNT/GCE is comparable to values reported for GCE, CNT/GCE and PHCS/GCE. The PHCS–CNT/GCE sensor responded linearly to tyrosine (Tyr) in the concentration of 1.0 × 10^–6 to 8.0 × 10^–4 M with detection limit of 3.0 × 10^–7 M at 3σ using amperometry. In addition, the PHCS–CNT/GCE displayed good reproducibility, high sensitivity and good selectivity towards the determination of Tyr, making it suitable for the determination of Tyr in clinical and medicine.     

Comparing the differential capacitance of two ionic liquid electrolytes: Effects of specific adsorption

The differential capacitance/potential curves of two ionic liquid (IL) electrolytes, 1-butyl-3-methyl-imidazolium hexafluorophosphate (BMIM⁺/PF₆⁻) and N-butyl-N-methyl-pyrrolidinium hexafluorophosphate (Pyr₁₄⁺/PF₆⁻) on a glassy carbon (GC) electrode were measured experimentally. The differential capacitance of BMIM⁺/PF₆⁻/GC is higher in the negative polarization, while the differential capacitance of Pyr₁₄⁺/PF₆⁻/GC is higher in the positive polarization, although both ILs are composed of common anions, with cations of similar ionic structures and diameters. Such an opposite trend may be understood in terms of the specific adsorption between BMIM⁺ and the GC electrode, caused by the π-stacking interaction between the aromatic imidazolium ring and the sp² graphite surface. The specific adsorption effectively shortens the electric double layer (EDL) thickness on the negatively charged electrode but elongates the EDL thickness on the positively charged electrode. Such an effect is manifested in the differential capacitance, with a higher value on the negative polarization branch than on the positive polarization branch. The impact of the specific adsorption is also seen from the positive shift of the potential of zero charge of BMIM⁺/PF₆⁻/GC in comparison with that of Pyr₁₄⁺/PF₆⁻/GC.     

Electrochemical Detection of Persulfate at the Modified Glassy Carbon Electrode with Nanocomposite Containing Nano‐Ruthenium Oxide/Thionine and Nano‐Ruthenium Oxide/Celestine Blue

The present study describes the fabrication of a sensitive amperometric sensor for the determination of persulfate. The immobilization surface was prepared by modifying a glassy carbon (GC) electrode with a nanocomposite containing ruthenium oxide (RuOx) nanoparticles and thionine (TH) or celestin blue (CB). The modified electrodes indicated excellent electrocatalytic activity toward persulfate reduction at a potential of +0.1 V. The proposed sensor showed detection limits of 1.46 µM for the GC/RuOx/TH modified electrode and 2.64 µM for the GC/RuOx/CB modified electrode. The sensitivities were obtained as 3 nA µM^?1 at a concentration range of 10 µM to 11 mM for the GC/RuOx/TH modified electrode and 1 nA µM^?1 at a concentration range of 10 µM to 6 mM for the GC/RuOx/CB modified electrodes.     

Fabrication of Chitosan‐Multiwall Carbon Nanotube Nanocomposite Containing Ferri/Ferrocyanide: Application for Simultaneous Detection of D‐Penicillamine and Tryptophan

We report a simple and effective strategy for fabrication of the nanocomposite containing chitosan (CS) and multiwall carbon nanotube (MWNT) coated on a glassy carbon electrode (GCE). The characterization of the modified electrode (CS‐MWNT/GC) was carried out using scanning electron microscopy (SEM) and UV–vis absorption spectroscopy. The electrochemical behavior of CS‐MWNT/GC electrode was investigated and compared with the electrochemical behavior of chitosan modified GC (CS/GC), multiwalled carbon nanotube modified GC (MWNT/GC) and unmodified GC using cyclic voltammetry (CV) and electron impedance spectroscopy (EIS). The chitosan films are electrochemically inactive; similar background charging currents are observed at bare GC. The chitosan films are permeable to anionic Fe(CN)₆^3?/4? (FC) redox couple. Electrochemical parameters, including apparent diffusion coefficient for the Fe(CN)₆^3?/4? redox probe at FC/CS‐MWNT/GC electrode is comparable to values reported for cast chitosan films. This modified electrode also showed electrocatalytic effect for the simultaneous determination of D‐penicillamine (D‐PA) and tryptophan (Trp). The detection limit of 0.9 μM and 4.0 μM for D‐PA and Trp, respectively, makes this nanocomposite very suitable for determination of them with good sensitivity.     

An enhanced Nonenzymatic Electrochemical Glucose Sensor Based on Copper‐Palladium Nanoparticles Modified Glassy Carbon Electrodes

Novel copper‐palladium nanoparticles modified glassy carbon electrodes (Cu−Pd/GC) with enhanced nonenzymatic sensing for glucose were facilely prepared by one‐step electrodeposition. The structure and composition of the prepared nanoparticles were characterized by XRD, SEM, TEM and EDS, respectively. The electrode modified process was characterized by electrochemical impedance spectroscopy. Cyclic voltammetry and chronoamperometric experiments were used to evaluate the electrocatalytic activities of the electrodes toward glucose. The surface morphology and the electrocatalytic activities of Cu−Pd/GC was compared to Pd and Cu nanoparticles modified glassy carbon electrodes (Pd/GC and Cu/GC), respectively. Thanks to homogeneous distribution of Cu−Pd nanoparticles and the synergistic effect of Cu and Pd atoms, Cu−Pd/GC exhibited the highest sensitivity (298 μA mM⁻¹ cm⁻²) and the widest linear amperometric response (0.01 mM to 9.6 mM, R²=0.996) toward glucose compared to Pd/GC and Cu/GC. The detection limit of Cu−Pd/GC was 0.32 μM (S/N=3). In addition, the as‐prepared Cu−Pd/GC glucose sensor also exhibited exceptional capabilities of anti‐interference, reproducibility and long‐term stability. The as‐prepared sensor was also evaluated for determination of glucose concentration in human blood serum samples, which exhibited high reliability and accuracy, having great potential in clinical application.     

Cyclic voltammetric investigation of Eu<Superscript>3+</Superscript> on a MWCNTs/SDS-modified glassy carbon (GC) electrode

Electrochemical reduction behavior of Eu³⁺ on a multi-walled carbon nanotubes (MWCNTs)/sodium lauryl sulfate (SDS) (MWCNTs/SDS)-modified glassy carbon (GC) electrode was investigated by cyclic voltammetry (CV). Results indicated that the electrochemical reduction process of Eu³⁺ at the MWCNTs/SDS-modified GC electrode is a quasi-reversible and diffusion-controlled process. The value of standard rate constant (k _s) at the MWCNTs/SDS-modified GC electrode was estimated to 1.96 × 10⁻² cm s⁻¹. CV studies showed that the electrochemical response of Eu³⁺ was directly related to the ratio of MWCNTs to SDS, and the tube diameter of MWCNTs had a slight influence on the electrochemical behavior of Eu³⁺, whereas the tube length. of MWCNTs had a strong influence. CVs results also proved that s-MWCNTs (with shorter tube length)-modified GC electrode showed better response to the electrochemical reaction of Eu³⁺.     

Regio-selective hydroxylation of gem-difluorinated octanes by alkane hydroxylase (AlkB)

gem-Difluoromethylene substituted molecules constitute a distinct class of fluorinated compounds. In this study, special chemistry has been developed for their preparation based on the highly selective terminal hydroxylation of these gem-difluorinated octanes by AlkB (alkane hydroxylase) from Pseudomonas putida Gpo1 to form gem-difluorinated octan-1-ols. The hydroxylation reaction is performed by whole-cell catalysis. Identification of the distal- and proximal-hydroxylation products was made by ¹H, ¹³C, and ¹⁹F NMR; GC and GC/MSD; and/or by comparison with authentic standards in GC. To the best of our knowledge, we have obtained the first synthesis of 2,2-, 3,3- and 4,4-difluorooctan-1-ols, from simple and inexpensive starting materials.     

Can gas chromatography combustion isotope ratio mass spectrometry be used to quantify organic compound abundance?

Quantifying the concentrations of organics such as phospholipid fatty acids (PLFAs) and n‐alkanes and measuring their corresponding ¹³ C/¹² C isotope ratios often involves two separate analyses; (1) quantification by gas chromatography flame ionisation detection (GC‐FID) or gas chromatography/mass spectrometry (GC/MS), and (2) ¹³ C‐isotope abundance analysis by gas chromatography/combustion/isotope ratio mass spectrometry (GC‐C‐IRMS). This requirement for two separate analyses has obvious disadvantages in terms of cost and time. However, there is a history of using the data output of isotope ratio mass spectrometers to quantify various components; including the N and C concentrations of solid materials and CO₂ concentrations in gaseous samples. Here we explore the possibility of quantifying n‐alkanes extracted from sheeps' faeces and fatty acid methyl esters (FAMEs) derivatised from PLFAs extracted from grassland soil, using GC‐C‐IRMS. The results were compared with those from GC‐FID analysis of the same extracts. For GC‐C‐IRMS the combined area of the masses for all the ions (m/z 44, 45 and 46) was collected, referred to as 'area all', while for the GC‐FID analysis the peak area data were collected. Following normalisation to a common value for added internal standards, the GC‐C‐IRMS 'area all' values and the GC‐FID peak area data were directly compared. Strong linear relationships were found for both n‐alkanes and FAMEs. For the n‐alkanes the relationships were 1:1 while, for the FAMEs, GC‐C‐IRMS overestimated the areas relative to the GC‐FID results. However, with suitable reference material 1:1 relationships were established. The output of a GC‐C‐IRMS system can form the basis for the quantification of certain organics including FAMEs and n‐alkanes. Copyright © 2011 John Wiley & Sons, Ltd.     

Properties of Poly(sodium 4‐styrenesulfonate)‐Ionic Liquid Composite Film and Its Application in the Determination of Trace Metals Combined with Bismuth Film Electrode

A new kind of bismuth film modified electrode to sensitively detect trace metal ions based on incorporating highly conductive ionic liquids 1‐butyl‐3‐methyl‐imidazolium hexafluorophosphate (BMIMPF₆) in solid matrices at glassy carbon (GC) was investigated. Poly(sodium 4‐styrenesulfonate) (PSS), silica, and Nafion were selected as the solid matrices. The electrochemical properties of the mixed films modified GC were evaluated. The electron transfer rate of Fe(CN)₆^4?/Fe(CN)₆^3? can be effectively improved at the PSS‐BMIMPF₆ modified GC. The bismuth modified PSS‐BMIMPF₆ composite film electrodes (GC/PSS‐BMIMPF₆/BiFEs) displayed high mechanical stability and sensitive stripping voltammetric performances for the determination of trace metal cations. The GC/PSS‐BMIMPF₆/BiFE exhibited well linear response to both Cd(II) and Pb(II) over a concentration range from 1.0 to 50 μg L^?1. And the detection limits were 0.07 μg L^?1 for Cd(II) and 0.09 μg L^?1 for Pb(II) based on three times the standard deviation of the baseline with a preconcentration time of 120 s, respectively. Finally, the GC/PSS‐BMIMPF₆/BiFEs were successfully applied to the determination of Cd(II) and Pb(II) in real sample, and the results of present method agreed well with those of atomic absorption spectroscopy.     

Selective Determination of Se4+ and Se6+ Using SPME and GC/MS

A method for the selective determination of Se⁴⁺ and Se⁶⁺ using solid phase microextraction (SPME) and GC/MS analysis is presented. Se⁴⁺ is selectively derivatized by reaction with 4,5-dichloro-1,2-phenylenediamine to form the corresponding piazselenolo complex, extracted by the SPME fiber, and determined by GC/MS. The RSD at a 5 μg/L concentration was 9.88% and the theoretical detection limit 6 ng/L. The method was employed to test real matrices; tap and river water were analyzed before and after spiking giving a recovery rate of 102% in river water and 97% in tap water.     

Voltammetric detection of riboflavin based on ordered mesoporous carbon modified electrode

The potential application of ordered mesoporous carbon (OMC)-modified glassy carbon electrode (OMC/GCE) in electrochemistry as a novel electrode material was investigated. X-ray diffraction, transmission electron micrographs, and cyclic voltammetry were used to characterize the structure and electrochemical behaviors of this material. Compared to GC electrode, the peak currents of potassium ferricyanide (K₃[Fe(CN)₆]) increase and the peak potential separation (ΔE _p) decreases at the OMC/GC electrode. These phenomena suggest that OMC-modified GC electrode possesses larger electrode area and faster electron transfer rate, as compared with bare GC electrode. Furthermore, riboflavin was detected using OMC/GC electrode in aqueous solutions. The results showed that, under an optimum condition (pH 7.0), the OMC/GC electrode exhibited excellent response performance to riboflavin in the concentration range of 4.0 × 10⁻⁷ to 1.0 × 10⁻⁶ M with a high sensitivity of 769 μA mM⁻¹. The detection limit was down to around 2 × 10⁻⁸ M. With good stability and reproducibility, the present OMC/GC electrode was applied in the determination of vitamin B₂ content in vitamin tablets, and satisfactory results were obtained.     

Influence of Metal Nanoparticles on the Electrocatalytic Oxidation of Glucose by Poly(NiIIteta) Modified Electrodes

Conductive polymeric [Ni^II(teta)]²⁺ (teta=C‐meso‐5,5,7,12,12,14‐hexamethyl‐1,4,8,11‐tetra‐azacyclotetradecane) films (poly(Ni)) have been deposited on the surface of glassy carbon (GC), Nafion (Nf) modified GC (GC/Nf) and Nf stabilized Ag and Au nanoparticles (NPs) modified GC (GC/Ag‐Nf and GC/Au‐Nf) electrodes. The cyclic voltammogram of the resulting electrodes, show a well defined redox peak due to oxidation and reduction of poly(Ni) system in 0.1 M NaOH. They show electrocatalytic activity towards the oxidation of glucose. AFM studies reveal the formation of poly(Ni) film on the modified electrodes. Presence of metal NPs increases electron transfer rate and electrocatalytic oxidation current by improving the communication within the Nf and poly(Ni) films. In the presence of metal NPs, 4 fold increase in current for glucose oxidation was observed.     

Electrocatalytic Dioxygen Reduction at Glassy Carbon Electrode Modified with Polyaniline Grafted Multiwall Carbon Nanotube Film

The work details the electrocatalysis of oxygen reduction reaction (ORR) in 0.5 M H₂SO₄ medium on a modified electrode containing a film of polyaniline (PANI) grafted multi‐wall carbon nanotube (MWNT) over the surface of glassy carbon electrode. We have fabricated a novel modified electrode in which conducting polymer is present as connected unit to MWNT. The GC/PANI‐g‐MWNT modified electrode (ME) is fabricated by electrochemical polymerization of a mixture of amine functionalized MWNT and aniline with GC as working electrode. Cyclic voltammetry and amperometry are used to demonstrate the electrocatalytic activity of the GC/PANI‐g‐MWNT‐ME. The GC/PANI‐g‐MWNT‐ME exhibits remarkable electrocatalytic activity for ORR. A more positive onset potential and higher catalytic current for ORR are striking features of GC/PANI‐g‐MWNT‐ME. Rapid and high sensitivity of GC/PANI‐g‐MWNT‐ME to ORR are evident from the higher rate constant (7.92×10² M^?1 s^?1) value for the reduction process. Double potential chronoamperometry and rotating disk and rotating ring‐disk electrode (RRDE) experiments are employed to investigate the kinetic parameters of ORR at this electrode. Results from RDE and RRDE voltammetry demonstrate the involvement of two electron transfer in oxygen reduction to form hydrogen peroxide in acidic media.     

Cu+ chemical ionization for analysis of hydrocarbons by gas chromatography/mass spectrometry

The use of copper ions for chemical ionization (CI) coupled with gas chromatography/mass spectrometry (GC/MS) of hydrocarbons is reported. Cu⁺?CI was performed in a high-pressure, fast atom bombardment ion source coupled with both a gas chromatograph and a mass spectrometer. The suitability of the Cu⁺?CI method is illustrated by the analysis of pure alkylbenzenes, alkylthiophenes, octenes, and by the analysis of a light mixture of aromatic hydrocarbons. The Cu⁺?CI/GC mass spectra display an abundant [M+⁶³Cu]⁺ ion, together with fragmentations, that are of structural interest. The detection limit for isobutylbenzene, taken as model compound, is 100 times lower than that for electron ionization.     

A Novel Enzymatic Glucose Biosensor and Nonenzymatic Hydrogen Peroxide Sensor Based on (3‐Aminopropyl) Triethoxysilane Functionalized Reduced Graphene Oxide

In the present study, a novel enzymatic glucose biosensor using glucose oxidase (GOx) immobilized into (3‐aminopropyl) triethoxysilane (APTES) functionalized reduced graphene oxide (rGO‐APTES) and hydrogen peroxide sensor based on rGO‐APTES modified glassy carbon (GC) electrode were fabricated. Nafion (Nf) was used as a protective membrane. For the characterization of the composites, Fourier transform infrared spectroscopy (FTIR), X‐ray powder diffractometer (XRD), and transmission electron microscopy (TEM) were used. The electrochemical properties of the modified electrodes were investigated using electrochemical impedance spectroscopy, cyclic voltammetry, and amperometry. The resulting Nf/rGO‐APTES/GOx/GC and Nf/rGO‐APTES/GC composites showed good electrocatalytical activity toward glucose and H₂O₂, respectively. The Nf/rGO‐APTES/GC electrode exhibited a linear range of H₂O₂ concentration from 0.05 to 15.25 mM with a detection limit (LOD) of 0.017 mM and sensitivity of 124.87 μA mM⁻¹ cm⁻². The Nf/rGO‐APTES/GOx/GC electrode showed a linear range of glucose from 0.02 to 4.340 mM with a LOD of 9 μM and sensitivity of 75.26 μA mM⁻¹ cm⁻². Also, the sensor and biosensor had notable selectivity, repeatability, reproducibility, and storage stability.     

The application of gas chromatography/atmospheric pressure chemical ionisation time‐of‐flight mass spectrometry to impurity identification in Pharmaceutical Development

Accurate mass measurement (used to determine elemental formulae) is an essential tool for impurity identification in pharmaceutical development for process understanding. Accurate mass liquid chromatography/mass spectrometry (LC/MS) is used widely for these types of analyses; however, there are still many occasions when gas chromatography (GC)/MS is the appropriate technique. Therefore, the provision of robust technology to provide accurate mass GC/MS (and GC/MS/MS) for this type of activity is essential. In this report we describe the optimisation and application of a newly available atmospheric pressure chemical ionisation (APCI) interface to couple GC to time‐of‐flight (TOF) MS. To fully test the potential of the new interface the APCI source conditions were optimised, using a number of standard compounds, with a variety of structures, as used in synthesis at AstraZeneca. These compounds were subsequently analysed by GC/APCI‐TOF MS. This study was carried out to evaluate the range of compounds that are amenable to analysis using this technique. The range of compounds that can be detected and characterised using the technique was found to be extremely broad and include apolar hydrocarbons such as toluene. Both protonated molecules ([M + H]⁺) and radical cations (M^+.) were observed in the mass spectra produced by APCI, along with additional ion signals such as [M + H + O]⁺. The technique has been successfully applied to the identification of impurities in reaction mixtures from organic synthesis in process development. A typical mass accuracy of 1–2 mm/zunits (m/z 80–500) was achieved allowing the reaction impurities to be identified based on their elemental formulae. These results clearly demonstrate the potential of the technique as a tool for problem solving and process understanding in pharmaceutical development. The reaction mixtures were also analysed by GC/electron ionisation (EI)‐MS and GC/chemical ionisation (CI)‐MS to understand the capability of GC/APCI‐MS relative to these two firmly established techniques. Copyright © 2010 John Wiley & Sons, Ltd.