Nutritional supplements cross-contaminated and faked with doping substances

Since 1999 several groups have analyzed nutritional supplements with mass spectrometric methods (GC/MS, LC/MS/MS) for contaminations and adulterations with doping substances. These investigations showed that nutritional supplements contained prohibited stimulants as ephedrines, caffeine, methylenedioxymetamphetamie and sibutramine, which were not declared on the labels. An international study performed in 2001 and 2002 on 634 nutritional supplements that were purchased in 13 different countries showed that about 15% of the nonhormonal nutritional supplements were contaminated with anabolic-androgenic steroids (mainly prohormones). Since 2002, also products intentionally faked with high amounts of 'classic' anabolic steroids such as metandienone, stanozolol, boldenone, dehydrochloromethyl-testosterone, oxandrolone etc. have been detected on the nutritional supplement market. These anabolic steroids were not declared on the labels either. The sources of these anabolic steroids are probably Chinese pharmaceutical companies, which sell bulk material of anabolic steroids. In 2005 vitamin C, multivitamin and magnesium tablets were confiscated, which contained cross-contaminations of stanozolol and metandienone. Since 2002 new 'designer' steroids such as prostanozol, methasterone, androstatrienedione etc. have been offered on the nutritional supplement market. In the near future also cross-contaminations with these steroids are expected. Recently a nutritional supplement for weight loss was found to contain the beta2-agonist clenbuterol. The application of such nutritional supplements is connected with a high risk of inadvertent doping cases and a health risk. For the detection of new 'designer' steroids in nutritional supplements, mass spectrometric strategies (GC/MS, LC/MS/MS) are presented.     

Analysis of doping control samples using supercritical fluid chromatography-tandem mass spectrometry: Ready for routine use

Supercritical fluid chromatography is proving to be a good separation and sample preparation tool for various analytical applications and, as such, has gained the attention of the anti-doping community. Here, the applicability of supercritical fluid chromatography hyphenated to tandem mass spectrometry for routine doping control analysis was tested. A multi-analyte method was developed to cover 197 drugs and metabolites that are prohibited in sport. More than 1000 samples were analyzed by applying a “dilute and inject” approach after hydrolysis of glucuronide metabolites. Additionally, a comparison with routinely used liquid chromatography-mass spectrometry was performed with 250 of the 1000 samples and a number of past positive anti-doping samples. It revealed some features where supercritical fluid chromatography-tandem mass spectrometry was found to be complementary or advantageous to liquid chromatography-mass spectrometry for anti-doping purposes, such as better retention of analytes that are poorly retained in reversed-phase liquid chromatography. Our results suggest that supercritical fluid chromatography-tandem mass spectrometry is sensitive (limit of detection <50% relevant minimum required performance level required by the World Anti-Doping Agency for anti-doping analysis), reproducible, robust, precise (analytes of interest area coefficient of variation <5%; retention time difference coefficient of variation <1%) and complementary to existing techniques currently used for routine analysis in the World Anti-Doping Agency accredited laboratories.     

Controlling the elution order of insulin and its analogs in sub-/supercritical fluid chromatography using methanesulfonic acid and 18-crown-6 as mobile phase additives

The purity analysis of therapeutic peptides can often be challenging, demanding the application of more than a single analytical technique. Supercritical fluid chromatography nowadays is a promising alternative to reversed-phase liquid chromatography, providing orthogonal and complementary information. This study investigated its applicability for the separation of human insulin, its analogs and degradation products. A previously published method development protocol for peptides up to 2000 Da was successfully applied to the higher molecular weight insulins (6 kDa). A single gradient method was optimized for all insulins using a Torus DEA column (100 × 3.0 mm, 1.7 μm), carbon dioxide and a modifier consisting of methanol/acetonitrile/water/methanesulfonic acid (65:35:2:0.1, v/v/v/v). Consecutively, the crown ether 18-crown-6, which is well known to complex charged lysine sidechains and other amino functionalities, was added to the modifier to evaluate its impact on selectivity. A decreased retention and a shift in the elution order for the insulins were observed. An inverse effect on retention was found when combined with a neutral stationary phase chemistry (Viridis BEH).     

Carbon-Carbon Bond Formation from Carbon Monoxide and Hydride: The Role of Metal Formyl Intermediates**

Current examples of carbon chain production from metal formyl intermediates with homogeneous metal complexes are described in this Minireview. Mechanistic aspects of these reactions as well as the challenges and opportunities in using this understanding to develop new reactions of CO and H₂ are also discussed.     

Beyond electronegativity and local hardness: Higher-order equalization criteria for determination of a ground-state electron density

Higher-order global softnesses, local softnesses, and softness kernels are defined along with their hardness inverses. The local hardness equalization principle recently derived by the authors is extended to arbitrary order. The resulting hierarchy of equalization principles indicates that the electronegativity/chemical potential, local hardness, and local hyperhardnesses all are constant when evaluated for the ground-state electron density. The new equalization principles can be used to test whether a trial electron density is an accurate approximation to the true ground-state density and to discover molecules with desired reactive properties, as encapsulated by their chemical reactivity indicators.     

Complexity of chaotic binary sequence and precision of its numerical simulation

Numerical simulation is one of primary methods in which people study the property of chaotic systems. However, there is the effect of finite precision in all processors which can cause chaos to degenerate into a periodic function or a fixed point. If it is neglected the precision of a computer processor for the binary numerical calculations, the numerical simulation results may not be accurate due to the chaotic nature of the system under study. New and more accurate methods must be found. A quantitative computable method of sequence complexity evaluation is introduced in this paper. The effect of finite precision is evaluated from the viewpoint of sequence complexity. The simulation results show that the correlation function based on information entropy can effectively reflect the complexity of pseudorandom sequences generated by a chaotic system, and it is superior to the other measure methods based on entropy. The finite calculation precision of the processor has significant effect on the complexity of chaotic binary sequences generated by the Lorenz equation. The pseudorandom binary sequences with high complexity can be generated by a chaotic system as long as the suitable computational precision and quantification algorithm are selected and behave correctly. The new methodology helps to gain insight into systems that may exist in various application domains such as secure communications and spectrum management.     

Zur Bestimmung des Gesamt-Kohlenstoffs in Kohlen und Bodenarten

Ohne Zusammenfassung     

Toward a semiempirical density functional theory of chemical binding

The new ideas ofbond electronegativity andbond hardness are introduced, and a semiempirical density functional approach to the theory of molecular electronic structure and chemical binding is outlined. There result effective electronegativity equalization procedures that permit calculation of binding energies as well as partial charges. By a modelling of the bond electronegativity and bond hardness, a density functional interpretation of earlier bond charge models is established. Some numerical results are given for diatomic molecules.Dedicated to Professor J. Koutecký on the occasion of his 65th birthday