Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography–mass spectrometry

Peptide quantification by liquid chromatography–mass spectrometry (LC–MS) combines the high resolving power of reversed-phase (RP) chromatography with the excellent selectivity and sensitivity of mass spectrometric detection. On the basis of comprehensive practical experience in the analysis of small molecules, pharmaceutical research is developing technologies for analysis of a growing number of peptidic drug candidates. This article is a detailed review of procedures based on LC–MS techniques for quantitative determination of peptides. With the focus on pharmaceutical applications several technologies for sample preparation, various aspects of peptide chromatography, important characteristics of ESI–MS, selectivity of MS-detection modes, the large variability of internal standards, and modern instrumentation are discussed. The demand for reliable, robust, sensitive, and accurate methods is discussed using numerous examples from the literature, complemented by experiments and results from our laboratory.     

Triolsulphonate derivatives of amino acids

The synthesis and chemical properties of a series of amino acid derivatives containing the thiolsulphonate functionality are described.     

Study of K−p→K1(890)n at 13 GeV

The results of a wire chamber spectrometer experiment studying $\text{K}$¹ (890) production in the reaction K^?p→ K^?π⁺n at 13 GeV are presented. Strong forward structure is observed for |t|< m²_π in the s-channel density matrix elements and differential cross section. These features are similar to those observed in π^?p→?⁰n data and are characteristics of π exchange. In contrast in the intermediate, |t| ～ 0.2 GeV², and large momentum transfer regions $\text{K}$¹ (890) production is demonstrated by the natural parity ??A₂ exchange contribution.     

Charge symmetry breaking in np-->dpi(0)

The forward-backward asymmetry in np-->dpi(0), which must be zero in the center-of-mass system if charge symmetry is respected, has been measured to be [17.2+/-8.0(stat)+/-5.5(syst)]x10(-4), at an incident neutron energy of 279.5 MeV. This observable is compared to recent chiral effective field theory calculations, with implications regarding the du quark mass difference.     

The role of magnesium in the susceptibility of soldiers to noise-induced hearing loss

A number of studies have demonstrated that magnesium, administered prophylactically, can reduce the amount of hearing loss resulting from noise exposure. This study explored the possible role of naturally occurring body magnesium concentration in susceptibility of soldiers to noise-induced hearing loss. Participants were 68 adult males who had received extensive noise exposure over several years as a result of training with weapon systems. Each participant provided a pure-tone audiogram, blood sample, and noise-exposure history. A variety of pure-tone indices was correlated with serum magnesium levels as determined by atomic absorption spectroscopy. No significant correlations were observed between any audiometric index and body magnesium. The results of this study, therefore, do not support the hypothesis that there is a strong association between naturally occurring body magnesium and susceptibility to noise-induced hearing loss.     

Phoneme boundaries in normal and hearing-impaired ears

Two experiments are reported which explore variables that may complicate the interpretation of phoneme boundary data from hearing-impaired listeners. Fourteen synthetic consonant-vowel syllables comprising a/ba-da-ga/ continuum were used as stimuli. The first experiment examined the influence of presentation level and ear of presentation in normal-hearing subjects. Only small differences in the phoneme boundaries and labeling functions were observed between ears and across presentation levels. Thus monaural presentation and relatively high signal level do not appear to be complicating factors in research with hearing-impaired listeners, at least for these stimuli. The second experiment described a test procedure for obtaining phoneme boundaries in some hearing-impaired listeners that controlled for between-subject sources of variation unrelated to hearing impairment and delineated the effects of spectral shaping imposed by the hearing impairment on the labeling functions. Labeling data were obtained from unilaterally hearing-impaired listeners under three test conditions: in the normal ear without any signal distortion; in the normal ear listening through a spectrum shaper that was set to match the subject's suprathreshold audiometric configuration; and in the impaired ear. The reduction in the audibility of the distinctive acoustic/phonetic cues seemed to explain all or part of the effects of the hearing impairment on the labeling functions of some subjects. For many other subjects, however, other forms of distortion in addition to reduced audibility seemed to affect their labeling behavior.