Abstract: A gas chromatographic mass spectrometric method for the quantitative determination of imipramine and its N-demethylated metabolite desipramine in plasma samples at the nanogram level is reported. The method involves derivatization of the extracted drugs with trifluoroacetylimidazole, a mild derivatizing reagent. Specificity is provided by selected ion recording of the [M + H]+ ions, formed upon chemical ionization with methane as reagent gas. Quantitation is achieved by stable isotope dilution techniques, using deuterium labeled analogs, prepared by acid-catalyzed exchange, as internal standards. Data on patient samples are presented.

Abstract: A gas-chromatographic procedure for acetaminophen is described in which the drug is chromatographed as the O-heptyl-N-methyl derivative. This derivative is prepared by a sequential alkylation procedure in which the phenolic hydroxyl group of the parent compound is alkylated off-column with heptyl iodide and the amide group is derivatized on-column by reaction with trimethylanilinium hydroxide. The internal standard, N-propionyl-p-aminophenol, is subjected to the same derivatization procedure. This gas-chromatographic procedure correlates well with conventional colorimetric and spectrophotometric procedures for acetaminophen and is more sensitive. Within-run precision (CV) was 2.0% at a serum concentration of 10.0 mg/liter (n = 10) and between-run precision was 4.0% over a period of eight months. This method is particularly applicable to studies of the pharmacokinetics of acetaminophen.

Abstract: A general derivatization method has been developed for both primary and secondary aminoalkyl-phosphonic acids. Derivatization is effected by reaction with trifluoroacetic acid and trifluoroacetic acid anhydride followed by esterification using ethereal diazo-n-butane. This method can be used for microgram quantities and permits ready characterization by both gas chromatography and gas chromatography mass spectrometry. The structure of this derivative has been verified by mass spectrometry and proton magnetic resonance. Fragmentation patterns were confirmed by high resolution mass spectrometry, isotope labeling and the formation of derivative analogs.

Abstract: Polyunsaturated fatty acids of human serum were analysed by combination gas-liquid chromatography and chemical ionization mass spectrometry, using isobutane as the reagent gas. The method described yielded the molecular ion of long chain unsaturated fatty acids as the base peak; these were weak or unobservable in the corresponding electron impact mass spectra. In the chemical ionization mass spectrometry, the derivatization with trimethylsilyl ether was demonstrated to be useful for the location of the double bonds of unsaturated fatty acids. Applied toteh serum polyunsaturated fatty acids, these methods have given identification of C18:4, C20:4, C20:5, C22:4, C22:5omega-6, C22:5omega-3, and C22:6.

Abstract: 1. The metabolism of debrisoquine sulphate in the dog has been studied and is similar to that in rat and man.2. Two acidic urinary metabolites, shown to be present in rat, dog and man, have been isolated from rat urine. After derivatization they were characterized by n.m.r. and mass spectroscopy as methyl 2-[2-(4,6-dimethylpyrimidylamino)-methyl]-phenylacetate and 2-[2-(4,6-dimethylpyrimidylamino)-ethyl]benzoate.

Abstract: Various methods for the separation of amino acids from brewing materials and subsequent analysis by gas chromatography have been examined. Separation of the amino acids by ion exchange chromatography followed by derivatization and gas chromatography of the trifluoracetyl n-butyl or heptafluorobutyl iso-amyl esters proved the most satisfactory methods to employ.

Abstract: The amino acid sequence of a polypeptide can be deduced by an identification of all the dipeptides obtained from a Dipeptidylaminopeptidase I hydrolysate of the original polypeptide and its des N-terminal amino acid derivative. The components of such dipeptide mixtures can be readily identified from the chemical ionization (helium) mass spectra of their N-ethoxycarbonylpropenyl methyl ester derivatives without prior separation. The pyrolytic conversion of N-protected peptide dimethyltrideuteromethyl anilinium salts to their methyl esters in the direct insertion probe of a mass spectrometer was found to be most suitable for the derivatization of such dipeptide mixtures.

Abstract: A method for the quantitative determination of several N-methylcarbamates in natural waters and the applicability of the derivative to soil samples using a previously published extraction procedure are described. After extraction of the carbamates from the substrate, the carbamates are hydrolyzed in a 10% methanol-potassium hydroxide solution to form the phenolic hydrolysis products, which are isolated and derivatized with pentafluorobenzyl (PFB) bromide to produce the PFB ether derivatives. The PFB derivatives are cleaned up and fractionated on a silica gel microcolumn and determined by electron capture gas-liquid chromatography (GLC). Eight organophosphate pesticides and 2 phthalate acid esters that hydrolyze to phenols or phthalic acid were evaluated as potential interferences and were found not to interfere with any of the carbamates tested. Quantitative determinations of 0.1 mug carbofuran and 3-ketocarbofuran and 0.5 mug carbaryl, metmercapturon, and Mobam in a 1 L water sample are possible. Propoxur was not determined at levels less than 1 mug/L due to the short GLC retention time of the derivative and interferences from the reagents at the lower levels.