Marianna Mák

Steroid epimers studied by different mass spectrometric methods.

The combined use of different mass spectrometric ionization methods and MS/MS techniques provide the possibility to differentiate between stereoisomers or epimers. In this paper the mass spectral decomposition of 11alpha- and 11beta-substituted estrans was studied. Distinctive stereochemical effects have been observed in their fast atom bombardment product ion spectra. In the electron ionisation (EI) mode, the 5alpha- and 5beta-hydroxylated compounds showed significant differences in the abundance of water elimination. Mass spectrometry has proved to be an effective tool when stereoisomer steroids are compared.

Fast atom bombardment mass spectrometry of quaternary salts of some aminoandrostanes

Abstract The fast atom bombardment (FAB) mass spectral features of pipecuronium bromide (Arduan), used in anaesthesiology as a neuromuscular blocking agent, and seventeen of its related mono-, bis- and tris-quaternary derivatives of general formula C n + (A − ) n ( n =1−3) were studied. The +FAB mass spectra of these ammonium salts were found to be very interesting and structurally informative: they exhibit abundant, stable C n + ions, i.e. C + , C 2+ and even C 3+ intact cations for mono-, bis- and trisquaternary salts, respectively. Primary and singly charged C n + (A − ) n −1 cluster ions were found to be dominant or significant in the spectra for all of these salts showing characteristic decomposition. The −FAB spectra display pronounced C n + (A − ) n +1 primary cluster ions with a low extent of fragmentation. 252 Cf plasma desorption mass spectra of these salts were found to be very similar to those obtained by FAB.

Metabolism of flumecinol in humans

1. The metabolism of 14C-flumecinol (3-trifluoromethyl-alpha-ethyl-benzhydrol) was studied in volunteers after a single oral dose of 100 mg (11.1 MBq; 300 microCi). Radioactivity excreted in urine was 78.8 +/- 6.0% of dose and in faeces was 12.0 +/- 5.3% dose in 120 h. 2. Unchanged flumecinol was not excreted in urine, but was present in faeces unconjugated (1.2% dose) and as conjugates of glucuronic and sulphuric acids (10.8% dose). 3. Enzymic hydrolysis showed that all urinary metabolites were conjugated with glucuronic and/or sulphuric acids (77.8% dose). Unconjugated urinary metabolites were not found. 4. The major route of flumecinol metabolism was hydroxylation of the alkyl side chain and/or the phenyl group followed by conjugation. 5. Both the CF3-group and the skeleton of the original compound remained intact during metabolism.

Hydrolytic behavior of 5α-hydroxy-11β- and 5β-hydroxy-11α-substituted 19-norsteroids

Abstract Teutsch G. and Belanger A. treated 5α,10α epoxides with Grignard-reagents catalyzed by copper(I) ions. The reaction with steroidal epoxides proceeded with complete regio- and stereospecificity, leading exclusively to the 11β-substituted compounds. According to our synthetic strategy, the 5,10 epoxide isomers were not separated; instead, the pure 11β, and in some cases, 11α-substituted molecules were isolated after the conjugate addition of the Grignard-reagents, followed by deketalization and dehydration. Surprisingly, appearance of a third compound was generally observed beside the expected deprotected products, and this compound turned out to have a 3-keto-5(10),9(11) structural unit. Starting from pure 3-ethylenedioxy-5α,10α-epoxy-estr-9(11)-ene-17-one and 3-ethylenedioxy-5β,10β-epoxy-estr-9(11)-ene-17-one, four model compounds were synthesized (11α- and 11β-{4-[1,1-(ethylenedioxy)-ethyl]phenyl}-estra-, as well as 11α- and 11β-cyclohexyl-estra-derivatives) to study the process of deprotection and dehydration. 3-keto-5(10),9(11)-derivatives were found to form after deketalization and dehydration only from 11α-substituted derivatives, while 11β-derivatives resulted in only the expected 3-keto-5,9-diene structure. After observing this remarkable difference between the behavior of 11α-, 11β-substituted isomers we decided to take a closer look at the processes of deketalization and dehydration. In order to carry out the hydrolysis under mild conditions, pyridinium paratoluenesulfonate, a weakly acidic salt, was applied. All the intermediate products observed by TLC were isolated. The outcome of the deprotection and elimination reactions can be rationalized by two factors: conjugation of olefins (with the 3-oxo-group or the 11-phenyl group) and orientation of groups to be eliminated.

Structure identification of synthetic human galanin using tandem mass spectrometry and in situ fast atom bombardment mapping

For the primary structure analysis of synthetic human galanin and several of its segments, the combination of the fast atom bombardment mapping and the tandem mass spectrometric method was applied. Multistep enzymic digestion performed in situ, i.e. directly on the probe tip and the subsequent high and low energy collision induced dissociation of the resulting hydrolytic products led to sufficient sequence information to elucidate and confirm the structure of the synthetic galanin derivatives.