Dominic M. Desiderio

Gas-liquid chromatography of trimethylsilyl and alkyl oxime-trimethylsilyl derivatives of some prostaglandins☆

TMS (trimethylsilyl), MO-TMS (methyl oxime-TMS), and EO-TMS (ethyl oxime-TMS) derivatives of several prostaglandins (A, B1, B2, E1, 8-iso-E1, E2 and 8-iso-E2) were prepared and their gas chromatographic properties examined on a moderately polar (OV-17) and a relatively non-polar (SE-30) stationary phase. Combined gas chromatography-mass spectrometry (GC-MS) using an LKB 9000 instrument was used to identify the different derivatives. Although the TMS derivatives are more easily prepared, the TMS derivatives of the PgE series are thermally somewhat unstable. Thus, MO-TMS and EO-TMS derivatives which exhibit more regular retention increments are more useful for analytical work. The EO-TMS derivatives may be useful in determining mass spectral fragmentation modes of the prostaglandin derivatives.

Formation of Fatty Acid Methyl Esters During Gas Chromatography Using Trimethylanilinium Hydroxide

Abstract Fatty acid methyl esters may be formed by dissolving the fatty acids in a 0.2 M solution of trimethylanilinium hydroxide in methanol and injecting the solution into a gas chromatograph. The reaction is rapid and quantitative, and the reagent appears to be less hazardous than diazomethane.

Utility of d4-PGE2 as an internal standard to quantify endogenous levels of PGE1, PGE2, 190H PGE1 and 190H PGE2 in human seminal fluid by GC-MS-SIM☆

Four prostaglandins-PGE1, PGE2, 19OH PGE1 and 19OH PGE2-were quantified in human seminal fluid by GC-MS-SIM using only the internal standard, d4-PGE2. Methods and calculations were developed to minimize errors inherent in using only one internal standard for quantifying four closely related prostaglandins. Preliminary data concerning the statistical significance of the difference found between PGE and 19OH PGE levels in fertile, azospermic and oligospermic men are reported.

Permethylation and mass spectrometry of intact ether glucuronides at the low nanomolar level

Abstract A group of steroid glucuronides and one drug glucuronide were permethylated with the dimethylsulfinylmethide anion and methyl iodide. All permethylated products were easily recognized as glucuronides from their mass spectra. Overmethylation was observed in those steroid samples which contained isolated or α , β -unsaturated ketones, but this did not hinder the interpretation of the spectra. The technique has further application for the study of drug metabolism.

Mass spectra of prostaglandins. I. Trimethylsilyl and alkyloxime-trimethylsilyl derivatives of prostaglandin A1

The mass spectra of the trimethylsilyl ester trimethylsilyl ether derivatives of prostaglandin A1 and of its O-ethyl and O-methyl oximes are reported and discussed. The high resolution spectra of these compounds are also considered. These spectra are compared with those of the corresponding d9-trimethylsilyl derivatives and of the selectively labeled trimethylsilyl ester d9-trimethylsilyl ethers. The 15-trimethylsilyloxy group is found to exert a strong fragmentation-directing effect, but the ring is very stable. A novel cyclisation process is invoked to account for the formation of certain fragment ions.

Pharmacokinetics of guanazole in man

Guanazole, 3,5‐diamino‐1,2,4‐triazole, synthesized nearly a century ago, has recently been shown to have antitumor properties. In patients with cancer, intravenous doses ranging from 3.5 to 10 gm per square meter of body surface area have been used. It was found that the 15 minute plasma level declines to one‐half in 1 to 2 hours. After 4 to 6 hours the plasma half‐life is 5 to 10 hours. The drug is eliminated almost quantitatively in the urine in 24 hours. No metabolites could be detected in the perfusate or bile of the isolated perfused rat liver preparation, suggesting that the drug itself rather than a metabolite is responsible for the antitumor activity.

Permethylation of methionine-containing oligopeptides for sequence analysis by mass spectrometry

Abstract Methionine-containing oligopeptides have been permethylated on the nanomolar level. Under the conditions developed, the formation of sulfonium iodide and cyclopropane derivatives during the permethylation reaction was avoided. The mass spectra presented here contain complete sequence information.

Derivatives for Characterization of Phosphoserine and Phosphothreonine by Gas Chromatography-Mass Spectrometry

Abstract Phosphoserine and phosphothreonine are reacted with bis(trimethylsilyl) acetamide and bis(trimethylsilyl)trifluoroacetamide to form trimethylsilyl derivatives. The derivatives obtained show good GC/MS characteristics and their mass spectra are readily applicable for identification of these two compounds. Another characteristic feature of the mass spectra of these derivatives is the presence in high abundance of several phosphorus-containing rearrangement ions.

Modified prostaglandins as internal standards for quantitative analysis of prostaglandins of the E series by combined gas chromatography-mass spectrometry.

Abstract ω-Homo-prostaglandin E1 and ω-nor-prostaglandin E2 are suitable standards for determination of prostaglandins of the E series by combined gas chromatography-mass spectrometry.

The Use of Mass Spectrometry in the Sequencing of Peptides of Biological Importance

Abstract A new permethylation reaction is described. This reaction is applicable for sequencing biologically important oligopeptides by means of mass spectrometry. The technique is illustrated-with a tetrapeptide that cannot be sequenced as easily by other methods.