Ionization methods, mass impurities

Experimental considerations Sample preparation and data evaluation are similar to membrane osmometry. Since there is no lower cut-off as in membrane osmometry, the method is very sensitive to low molar mass impurities like residual solvent and monomers. As a consequence, the method is more suitable for oligomers and short polymers with molar masses up to (M)n 50kg/mol. Today, vapour pressure osmometry faces strong competition from mass spectrometry techniques such as matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) [20,21]. Nevertheless, vapour pressure osmometry still has advantages in cases where fragmentation issues or molar mass-dependent desorption and ionization probabilities come into play. 

Check which ionization method was used and examine the general appearance of the mass spectrum. Is the molecular ion peak intensive (as with aromatic, heterocyclic, polycyclic compounds) or weak (as with aliphatic and multifunctional compounds) Are there typical impurities (solvent, grease, plasticizers) or background signals (residual air, column bleed in GC-MS) ... 

MS operation High vacuum in mass analyser (< 10 Pa) Free choice of ionization method (El, Cl or other) Free choice of Cl reagent gas conditions Both positive and negative ion mode Low interference from solvents and solvent impurities... 

Poly(2,2,4-trimethyl-l,2-dihydroquinoline), an oligomeric antioxidant for rubber, is a typical example for this ionization method. Figure 6.3 shows the FD mass spectrum of a poly-TMDQ sample. Molecular ions for "normal" oligomers (M = 173n) are observed, along with minor peaks due to impurities (with differing end-groups) from the synthesis. 

The formation of complexes between analytes and metal (-containing) ions is commonly observed and used in other methods of ionization. ESI mass spectra of organic compounds very often display adducts with Na and K+ ions. Solvents, glassware, and impure chemicals are common sources of these ions. Intentional doping of solutions by alkali-metal ions in ESI is widely used to improve the ionization of (non-polar) analytes, and to determine the number of mobile hydrogen atoms in molecules. 

Siegel MW, Fite WL. Terminal ions in weak atmospheric plasmas. Applications of atmospheric pressure ionization to trace impurity analysis in gases. J Phys Chem. 1976 80 2871-81. Sunner J, Ikonomou MG, Kebarle P. Sensitivity enhancements obtained at high temperatures in atmospheric pressure ionization mass spectrometry. Anal Chem. 1988 60 1308-13. Thomson BA. Micro and nano-electrospray ionization techniques. In Gross M, Caprioli R, editors. Encyclopedia of mass spectrometry Vol6. Ionization methods. Oxford Elsevier, 2007. pp. 435 4. 

We predict that more and more noncovalent complexes will be analyzed by mass spectrometry in the future. Complexes with high mass and from complicated protein extracts will be characterized the latter will require a high tolerance for impurities during the ionization step to be analyzed successfully. For this purpose, MALDI ionization with its simplicity, high speed, and high salt tolerance may be the ionization method of choice. ESI, as the softest of the modem soft ionization methods (and its variants), is well-suited to obtain... 

For confirmatory assay, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is becoming more frequently used in the analysis of OTC owing to its high sensitivity and ability. Electrospray ionization (ESI) [55-57] and atmospheric pressure chemical ionization (APCI) [41] methods combined with tandem mass spectrometry are favored because of their higher sensitivity and better reproducibility. Hamscher et al. [58] developed a method for the determination of persistent TC residues in soil fertilized with manure by HPLC tandem mass spectrometry, MS-MS, and confirmation by MS-MS-MS. Zhu et al. [59] developed an LC-tandem mass spectrometry for the analysis of common tetracyclines in water. The detection limit for oxytetracycline was 0.21 pg/L. Lykkeberg et al. [60] used LC-MS/MS for determination of oxytetracycline and its impurities EOTC, TC, ETC, ADOTC, oc-AOTC, and /i-AOTC. 

Pluym et al. compared the use of CE to that of HPLC in chemical and pharmaceutical quality control. They stated that CE could be considered as a complementary technique to HPLC because of its large separation capacity, its simplicity, and its economical benefits. Jimidar et al. decided that CE offers high separation efficiency and can be applied as an adjunct in HPLC method validation. Mol et al. evaluated the use of micellar electrokinetic chromatography (MEKC) coupled with electrospray ionization mass spectrometry (ESI—MS) in impurity profiling of drugs, which resulted in efficient separations. 

Vassort, A., Barrett, D. A., Shaw, P. N., Ferguson, P. D., and Szucs, R. (2005). A generic approach to the impurity profiling of drugs using standardized and independent capillary zone electrophoresis methods coupled to electrospray ionization mass spectrometry. Electrophoresis 26, 1712-1723. 

The more advanced instrumental methods of analysis, including GC, for the detection and identification of expls are presented (Ref 90) Pyrolysis of expls in tandem with GC/MS was used for the identification of contaminant expls in the environment (Ref 108). Isomer vapor impurities of TNT were characterized by GC-electron capture detector and mass spectrometry (Ref 61). Volatile impurities in TNT and Comp B were analyzed using a GC/MS the GC was equipped with electron capture and flame ionization detectors (Ref 79). The vapors evolved from mines, TNT, acetone, toluene, cyclohexanone and an organosilicon, were analyzed by GC/MS (Ref 78). Red water produced by the sellite purification of crude TNT was analyzed by GC/MS for potentially useful organic compds, 2,4-dinitrotoluene, 3- and 4-sulfonic acids (Ref 124). Various reports were surveyed to determine which methods, including GC/MS, are potential candidates for detection of traces of TNT vapors emitted from land mines factors influencing transportability of TNT vapors thru soil to soil/air interface are dis-... 

The kinetic method provides an alternative to equilibrium measurements for the determination of gas-phase thermochemical properties. It has been applied more and more in thermochemical data determination mainly because of its ability to measure very small energy differences and its simplicity. Indeed, it can be executed easily on any tandem mass spectrometer. Furthermore, this method is sensitive and is applicable with impure compounds. Its applications are broad, covering thermochemical properties in the gas phase such as proton affinity [46], electron affinity [47], metal ion affinity [48], ionization energy [49], acidity [50] or basicity [51], In addition to the determination of thermochemical data, the kinetic method has also been applied in structural and chemical analysis such as chiral distinctions. This method is able to distinguish enantiomers and to measure precisely enantiomeric ratios [52],... 

Electrospray ionization with the high resolving power of Fourier transform mass spectrometry (FTMS) makes possible the detection of adducts and subpicomole impurities that confuse lower resolution measurements, as shown in Figure 8.30. This method achieves accurate determination of molecular weights (<0.002 %) and permits the verification of 50-100-mer DNA and RNA sequences. [169,170]... 

The basic NR mass spectrum contains information on the fraction of undissociated (survivor) ions and also allows one to identify dissociation products that are formed by purely unimolecular reactions. NRMS thus provides information on the intrinsic properties of isolated transient molecules that are not affected by interactions with solvent, matrix, surfaces, trace impurities, radical quenchers, etc. However, because collisional ionization is accompanied by ion excitation and dissociation, the products of neutral and post-reionization dissociations overlap in the NR mass spectra. Several methods have been developed to distinguish neutral and ion dissociations and to characterize further short lived neutral intermediates in the fast beam. Moreover, collisionally activated dissociation (CAD) spectra have been used to characterize the ions produced by collisional reionization of transient neutral intermediates [51]. This NR-CAD analysis adds another dimension to the characterization of neutral intermediates, because it allows one to uncover isomerizations that do not result in a change of mass and thus are not apparent from NR mass spectra alone. 

The most frequently chosen method for compound characterization in the pharmaceutical industry is LC/MS [6]. Replacing flow injection by a chromatographic separation prior to MS analysis offers three major advantages i) impurities or by-products are separated in time from the product of interest, rendering a purity assessment of the sample possible ii) ionization suppression of the compound of interest by salts, detergents, or by-products is avoided iii) the interpretation of mass spectra of pure compounds is much easier than the MS analysis of mixtures. Combinations of separation techniques with mass spectrometry have been reviewed recently by Tomer [39]. 

The most-used spectroscopic method in drug analysis is mass spectrometry (MS). It allows (depending on the ionization technique) measurement of impurities at the nanogram or picogram level if an ion bombarding technique is used, even... 

A problem which arises after cleavage not only from polystyrene-based polymeric carriers is the presence of impurities derived presumably from linker or resin components [57]. The occurrence of these impurities hampers routine product analysis and may have considerable influence also on the screening assay. In the mass spectrometric analysis, they can compete with poorly ionizable products, thus inhibiting a reliable analysis. At worst, they may even preclude detection of the expected compound, leading to a misinterpretation of the synthesis results. It has been found that the extraneous signals in the mass spectra are primarily dependent upon the type of resin used. Differences between analogous resins from different suppliers, or even different charges are also observed. As yet, it has not been possible to characterize these impurities with the methods of mass spectrometry and NMR. 

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