Evaluation of analytical instrumentation. Part XIX CHNS elemental analysers

The reports of this series tabulate a number of features of analytical instruments that should be considered when making comparison between various systems. Scoring these features in a rational manner allows a scientific comparison to be made between instruments as an aid to selection. This is the XIXth report of the series and deals with CHNS elemental analysers.     

Evaluation of analytical instrumentation. Part XXII Instrumentation for liquid chromatography/mass spectrometry

The reports of this series tabulate a number of features of analytical instruments that should be considered when making comparison between various systems. Scoring these features in a rational manner allows a scientific comparison to be made between instruments as an aid to selection. This is the XXIInd report of the series and deals with instrumentation for liquid chromatography/mass spectrometry.     

Evaluation of analytical instrumentation. Part XX Instrumentation for energy dispersive X-ray fluorescence spectrometry

The reports of this series tabulate a number of features of analytical instruments that should be considered when making comparison between various systems. Scoring these features in a rational manner allows a scientific comparison to be made between instruments as an aid to selection. This is the XXth report of the series and deals with instrumentation for energy dispersive X-ray fluorescence spectrometry.     

Second- and higher-order data generation and calibration: A tutorial

An introduction to multi-way calibration based on second- and higher-order data generation and processing is provided, with emphasis on practical experimental aspects. After a discussion concerning a proper nomenclature scheme, a suitable classification of the obtainable data, and the general features of the available algorithms and their underlying models, a series of examples is discussed in detail, with the purpose of illustrating the great potentiality of the field for the analytical community. Emphasis is directed toward the most popular multi-way data, i.e., second-order or matrix data, which can be conveniently measured in a variety of instruments. Third-order data are being increasingly studied and are also discussed, along with the less explored field of fourth-order data. The estimation of figures of merit, which analysts need to report during method development, is now sufficiently mature to be provided for the general audience.     

Synthesis of second-generation sansalvamide A derivatives: novel templates as potential antitumor agents

We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.     

Molecular design based on 3D pharmacophores. Applications to 5-HT7 receptors

A definition of a pharmacophore for the 5-HT7 antagonists was carried out by searching the common chemical features of selective antagonists from the literature. A molecular design is described by analyzing the differences between this new pharmacophore and three other 3D serotonin pharmacophores previously described. This comparison led to the synthesis of a new series of potent 5-HT7 antagonists.     

Mass measurement accuracy comparisons between a double-focusing magnetic sector and a time-of-flight mass analyzer

We report a direct comparison of the mass measurement accuracies (MMAs) obtained on different mass spectrometry instrument types; a magnetic sector as the 'gold standard' and an electrospray ionization time-of-flight (ESI-TOF) instrument. Sixty samples, obtained from the Department of Chemistry at North Carolina State University, were analyzed on each instrument. Data are presented and compared between the different instruments. The average absolute MMAs achieved for the magnetic sector and Agilent ESI-TOF mass spectrometers were 3.0 and 1.1 ppm, respectively.     

A novel tandem quadrupole mass spectrometer allowing gaseous collisional activation and surface induced dissociation.

A novel tandem quadrupole mass spectrometer is described that enables gaseous collision-induced dissociation (CID) and surface-induced dissociation (SID) experiments. The instrument consists of a commercially available triple quadrupole mass spectrometer connected to an SID region and an additional, orthogonal quadrupole mass analyser. The performance of the instrument was evaluated using leucine-enkephalin, allowing a comparison between CID and SID, and with previous reports of other SID instruments. The reproducibility of SID data was assessed by replicate determinations of the collision energy required for 50% dissociation of leucine-enkephalin; excellent precision was observed (standard deviation of 0.6 eV) though, unexpectedly, the reproducibility of the equivalent figure for CID was superior. Several peptides were analysed using SID in conjunction with liquid secondary-ion mass spectrometry or electrospray; a comparison of the fragmentation of singly protonated peptide ions and the further dissociation of y-type fragments was consistent with the equivalence of the latter fragments to protonated peptides. Few product ions attributable to high-energy cleavages of amino acid side-chains were observed. The SID properties were investigated of a series of peptides differing only in the derivatization of a cysteine residue; similar decomposition efficiencies were observed for all except the cysteic acid analogue, which demonstrated significantly more facile fragmentation.     

Static SIMS studies of the oxides and hydroxides of aluminium

The degree of hydroxylation or hydration of aluminium surfaces has been examined by static secondary ion mass spectroscopy (SSIMS). The SSIMS spectra of a series of aluminium oxide, oxyhydroxide and hydroxide surfaces have been obtained using instruments in three configurations. Similarities were observed in both negative and positive secondary ions spectra. Even though a direct comparison of the relative intensities cannot be made from one instrument to the other, a similar ranking of the various aluminium hydroxylation states was observed. Several ranking methods are discussed, as well as the similarities and differences observed while using the three instruments. Similar secondary ions were detected whatever the degree of hydroxylation of the aluminium oxide. This argues in favour of the formation of fragments by the combination of individually sputtered atoms or clusters to form the more stable secondaries, rather than the kick-off of 'structure-related' clusters originating directly from the upper surface layer.     

Factors determining the performance of triple quadrupole, quadrupole ion trap and sector field mass spectrometers in electrospray ionization tandem mass spectrometry of oligonucleotides. 1. Comparison of performance characteristics

The performance of triple-stage quadrupole (TSQ), quadrupole ion trap (QIT), and double focusing sector field (DFSF) mass spectrometers for the generation of fragment ions to obtain sequence information about oligonucleotides was compared. Upon electrospray ionization (ESI), the charge-state distribution of candidate precursor ions not only varied significantly with the type of mass spectrometer, but also with the size and sequence of the investigated oligonucleotides. While concentration limits of detection for an octanucleotide were in the 100 pmol/L range on the QIT and in the 5-10 nmol/L range on the TSQ and DFSF instruments, those of a 24-mer were in the 2-13 nmol/L range on all three instruments. Reproducibility of mass determination, an important prerequisite for reliable identification of fragment ions, was highest on the TSQ with 0.0037% relative standard deviation over three days. Finally, the tandem mass spectra of a dimethoxytritylated pentanucleotide recorded on the three instruments were compared. Relatively simple spectra dominated by complete series of fragment ions of the (a-B) and w type were obtained on the QIT. Complete series of (a-B) and w ions were also observed on the TSQ. However, additional fragments belonging to the b, c, d, x and z series were found in the spectrum. In the spectrum recorded after in-source fragmentation in the DFSF, only fragments corresponding to the loss of a nucleobase and a complete series of w ions were observed. All three mass spectrometers were suitable for the generation of fragment ions, from which the complete nucleotide sequence of the pentanucleotide could be deduced.     

A comparison of the performance of calorimeters

Isothermal calorimetry is finding extensive application in a number of research areas. This popularity is reflected in the number of commercially available instruments which are capable of yielding a variety of thermodynamic and kinetic parameters. Whilst there has been much discussion of ways in which to validate any values returned from these instruments very little has been done quantitatively to compare the relative performances of different instruments. This paper highlights the use of a test and reference reaction quantitatively to compare the performance of three instruments (Thermometric TAM, THT μRC and a Setaram HSDSC III); the specifications of these instruments provide a range from high-sensitivity, long equilibration time to lower-sensitivity, short equilibration time. The comparison is made through a statistical analysis of values returned for the rate constant, enthalpy of reaction and activation energy for the base catalysed hydrolysis of methyl paraben. The statistical analysis from the data set discussed here indicates that there is no significant difference between the returned thermodynamic and kinetic parameters from the TAM and μRC. The analysis revealed however that the HSDSC returns values for the rate constant which are significantly different from both the TAM and μRC, although it is noted that this instrument was not specifically designed to operate in a step-isothermal mode and that it was possible to apply a correction to the data. In all cases the enthalpy data returned from all instruments were statistically similar although the μRC and HSDSC returned values which were, for the rate constant and activation energy, less precise than those obtained from the TAM. As well as highlighting the importance of using test and reference reactions, this study also shows that proper instrument selection is an important factor when designing a calorimetric experimental series.     

Isotopic metrology of carbon dioxide. II. Effects of ion source materials,conductance, emission,and accelerating voltage on dual-inlet cross contamination

We report high-precision isotopic carbon dioxide measurements, made before and after ion source modification to gas isotope ratio mass spectrometry (IRMS) instruments. Measurement protocols were designed to explore the effects of ion source material substitution, source conductance, inlet pressure, electron emission, acceleration potential, and inlet changeover equilibration time. After modification of the IRMS instruments at the National Institute of Standards and Technology (NIST) and the Max-Planck-Institute for Chemistry (MPI-Mainz), immediate changes were observed. At NIST, measurements were no longer sensitive to inlet equilibration times greater than 15 s, and different settings of ion source conductance resulted in delta(13)C shifts of about 0.04 per thousand per 10 per thousand measurement difference between sample and reference, a five-fold improvement. No significant changes in machine performance were observed after a month of use. After a year, performance had degraded slightly, but was controlled by ion source cleaning and the use of low-energy ion acceleration to minimize sputtering. At MPI-Mainz, results were very similar. We report cross-contamination coefficients measured since 1996, and discuss the role of adsorption, ion implantation, and sputtering on cross contamination in mass spectrometry systems. We recommend that users of high-precision IRMS instruments test for and minimize the effects described.     

Volume calibration of 1000 μl micropipettes. Inter-laboratory comparison

A EUROMET comparison “volume calibration of 1000 μl micropipettes”, between six national metrology institutes (NMIs), was performed during 2006 with the purpose of comparing results and uncertainty calculations. The objective of this paper is to describe the volume measure instruments, the model, the method, and to discuss the results and its associated uncertainties presented by each participating NMI.     

The development and inter-laboratory verification of LC-MS libraries for organic chemicals of environmental concern

The development, verification, and comparison study between LC-MS libraries for two manufacturers’ instruments and a verified protocol are discussed. Compounds in the libraries are among those considered by the U.S. EPA Office of Water as threats to drinking water including pesticides, drugs of abuse, and pharmaceuticals. The LC-MS library protocol was verified through an inter-laboratory study that involved Federal, State, and private laboratories. The results demonstrated that the libraries are transferable between the same manufacturer's product line, and have applicability between manufacturers. Although ion abundance ratios within mass spectra were shown to be different between the manufacturers’ instruments, the NIST search engine match probability was at 96% or greater for 64 out of 67 compounds evaluated.     

Internet-assisted exercises in structural analysis

In this report we describe our experience in the analytical chemistry curriculum of teaching spectrometer principles and preparing spectroscopy laboratory exercises by means of virtual instruments. The benefits of the intensified preparation of laboratory exercises by virtual instruments will be evaluated with respect to the subsequent handling of real instruments. The utilization of in-house electronic media with Internet resources for elucidation and verification of a structural assignment will also be considered.     

A method for monitoring and controlling reproducibility of intensity data in complex electrospray mass spectra: A thermometer ion-based strategy

Reproducibility in mass spectral data is important in both biomarker discovery and spectral database searching. We report a strategy, employing a series of substituted benzylpyridinium thermometer ions that can be used to monitor changes in performance of multiple aspects of an electrospray ionization source that impact the intensity axis of a spectrum. Performance attributes, which could confound even isotope-based quantification strategies, are readily assessed using a mixture of thermometer ions. Based on the observed behavior of the ions, a procedure is proposed for monitoring instrument performance and compensating for factors that affect reproducibility across both time and instruments.     

Standardization of Raman spectra for transfer of spectral libraries across different instruments

In this paper we evaluate methods for standardization of Raman spectra that are required to improve spectral correlation computations between spectra measured on different instruments. Five commercially-available 785 nm Raman spectrometers from different vendors were included in the study. These spectrometers have diverse specifications and performance levels and range in size from laboratory-based instruments to field-deployable portable and handheld platforms. Since each Raman spectrometer has different characteristics, spectra obtained on one instrument cannot readily be compared to a library acquired on a different instrument without performing various types of spectral corrections (standardization). We outline a procedure that combines previously established Raman shift and intensity correction protocols with a resolution matching step to facilitate the comparison of a centralized master library with spectra acquired on different geographically distributed Raman spectrometers. The standardization procedure is effective in reducing the inherent instrument-to-instrument variability so that spectra from different spectrometers can be compared and reliable results obtained using library-based spectral correlation methods. The findings have important implications for the ability to transfer Raman spectral libraries between instruments.     

A novel multifunctional labeling reagent for enhanced protein characterization with mass spectrometry.

Individual peptides with lysine at the C-terminus as well as protein tryptic digests were reacted with 2-methoxy-4,5-dihydro-1H-imidazole, converting lysine residues to their 4,5-dihydro-1H-imidazol-2-yl derivatives. The mass spectra of derivatized digests exhibit a greater number of more intense features than their underivatized counterparts, thus increasing the information obtained in peptide mapping experiments. Additionally, MS/MS spectra of the derivatized peptides are greatly simplified in comparison to their native species, yielding primarily an easily interpretable series of y-ions. Finally, this novel label also enables differential quantitation studies, as a stable isotopic form containing four deuterium atoms can readily be produced.     

New aspects of thermal analysis,Part I. Resolution of DSC and means for its optimization

The definitions of the temperature resolution, the so-called resolution of DSC instruments given in literature are discussed. A new definition of the resolution for DSC instruments is presented and outlined. The main characteristic introduced in this new definition is a minimum between two caloric events as a prerequisite of an existing resolution. Possible candidates of test substances have been evaluated. The oligomer n-hexatriacontane is revealing an interesting phenomenon, namely a lambda transition which is in the peak temperature only 2 K lower than the melting temperature of 76°C. The substance was selected as an ideal test substance for the quantification of the resolution of DSC instruments. The lambda transition is a second order process which may reach under certain conditions the saturation of the occurring molecular dislocation within 0.2 K, and after saturation the heat flow rate drops sharply down. Investigations concerning the main characteristics of n-hexatriacontane in respect to the temperatures of transition (lambda transition and melting), to the involved enthalpies, and to the resolution factors were performed as functions of the sample mass and the heating rate. The importance of relevant evaluation procedures increasing the resolution factors of DSC curves are discussed and these procedures are integrated into the testing of the resolution. The necessity for widening the experimental scope from instruments to evaluation procedures is forced by the existence of instruments with built-in signal treatments based on electronic devices and software procedures. A comparison with literature data is outlined for all of the mentioned characteristic values of n-hexatriacontane. This revised version was published online in August 2006 with corrections to the Cover Date.     

Alternating copolymerization of polar vinyl monomers in the presence of zinc chloride. II. Properties of acrylonitrile–styrene copolymer

The properties of the acrylonitrile–styrene copolymer prepared in the presence of zinc chloride were investigated in comparison with those of a copolymer having the same overall composition and prepared by the ordinary radical procedure. The characteristics of the polymer prepared with ZnCl₂ were as follows: (1) less coloration by alkali treatment, (2) less coloration by thermal treatment and (3) higher glass transition temperature. These features may be attributed principally to the structure of the copolymer, which has more unlike bonds and less long sequences as described in the first article of this series. The effects of residual salt in the copolymer on the properties were also investigated.