R.N. Stillwell

Liquid chromatograph—mass spectrometer—computer analytical systems: A continuous-flow system based on atmospheric pressure ionization mass spectrometry

Abstract Atmospheric pressure ionization (API) mass spectrometry is a novel form of mass spectrometry in which ions are generated in a reaction chamber external to the low-pressure region of a quadrupole mass spectrometer. Using this ionization technique a liquid chromatograph—mass spectrometer analytical system was constructed. The entire effluent stream from the chromatograph is vaporized throught the API source. The primary ionization source for this work was a corona discharge The very high ion densities generated by the corona discharge extend the linear range of the API source into the microgram region.

Atmospheric Pressure Ionization Mass Spectrometry

Abstract Atmospheric pressure ionization (API) mass spectrometry is a novel form of mass spectrometry in which the ionization process is carried out in a reaction chamber external to the mass analyzer region. The mass analyzer serves as a device to detect positive or negative ions present in the reaction chamber, which is maintained at atmospheric pressure.

Atmospheric pressure ionization mass spectrometry : Studies of negative ion formation for detection and quantification purposes

The analytical system described here consists of a gas chromatograph, an atmospheric pressure ionization mass spectrometer designed for operation in the negative ion mode, and a computer. The gas stream from the gas chromatograph is split in order to obtain concurrent but separate detection with a standard electron capture detector and with the mass spectrometer. The ion source of the mass spectrometer is also a duplicate of the standard electron capture detector, so that simultaneous monitoring of the ions and monitoring of the electron capture detection response can also be carried out for the reaction chamber. Negative ions observed under atmospheric pressure ionization conditions are almost always anions of strong gas phase acids. These may be formed by reaction with a gas phase basic ion, or by electron capture reactions. A few organic compounds form stable radical M− ions. Most pesticides, herbicides and fungicides, as well as numerous toxic compounds that are now environmental hazards, form stable anions and show an electron capture response. Most ordinary organic compounds do not form stable negative ions at atmospheric pressure and do not show an electron capture response. The results suggest that an analytical system of this kind will be useful for the detection and quantification of many environmentally hazardous compounds.

Characterization of metabolites of steroid contraceptives by gas chromatography and mass spectrometry

Abstract Metabolites isolated from human urine after oral administration of dimethisterone (6α-methyl-17α-(1-propynyl)-17β-hydroxy-4-androsten-3-one) and norethisterone (17α-ethynyl-17β-hydroxy-4-estren-3-one) were identified by gas chromatography and mass spectrometry. The major metabolite of dimethisterone is 6α-methyl-17α-(1-propynyl)-5β-androstane-3α, 17β-diol. The major urinary metabolites of norethisterone are 17α-ethynyl-5β-estrane-3α, 17β-diol and 17α-ethynyl-5α-estrane-3α, 17β-diol. The drug metabolites can be readily differentiated from urinary metabolites of endogenous steroids by both gas Chromatographic retention data and mass spectrometry.

The use of stable isotopes in gas chromatography-mass spectrometric studies of drug metabolism.

Abstract Internal reference compounds labeled with stable isotopes have been used to quantify drugs and drug metabolites in urine, plasma and breast milk. [2,4,5-13C3]Diphenylhydantoin, [2,4,5-13C3]phenobarbital and [1-C2H3]valium have been used to quantify diphenylhydantoin, phenobarbital and valium, respectively; [2,4,5-13C3]pentobarbital has been used to quantify amobarbital, secobarbital, butabarbital and pentobarbital. Analyses have been carried out in the picogram to nanogram range by selective ion detection with two gas chromatograph—mass spectrometer—computer systems. Instrumental measurements with picogram samples have also been made using an atmospheric pressure ionization mass spectrometer.

The use of gas chromatographic-mass spectrometric-computer systems in pharmacokinetic studies

Pharmacokinetic studies involving plasma, urine, breast milk, saliva and liver homogenates have been carried out by selective ion detection with a gas chromatographic-mass spectrometric-computer system operated in the chemical ionization mode. Stable isotope labeled drugs were used as internal standards for quantification. The half-lives, the concentration at zero time, the slope (regression coefficient), the maximum velocity of the reaction and the apparent Michaelis constant of the reaction were determined by regression analysis, and also by graphic means.

Plasma Desorption Ionization Mass Spectra of Unconjugated Human Steroids

Abstract Steroids, including cortisone, Cortisol, aldosterone, cortol, preg-nanediol, androsterone and 4-androsten-3, 17-dione can be ionized directly, without derivative formation, by plasma desorption ionization to give characteristic mass spectra. The ion products, with isobutane as the reagent gas, indicate the nature of the functional groups and the molecular formula; the spectra are similar to those obtained by chemical ionization methods.

Gas chromatographic-mass spectrometric-computer methods in the study of drug metabolism

The computer-assisted interpretation of repetitively scanned mass spectra can be of great value in the analysis of a complex mixture even in the absence of a library of reference spectra. We have written a set of interpretation programs for a PDP11/45 laboratory computer. A file structure is used that combines economy of storage with ease of creation and retrieval. User interaction is by a simple command language implemented by an interpreter. The program structure is such that additional functions can be added easily.

Gas-Phase Analytical Methods. Mass Spectrometry and GC-MS-COM Analytical Systems

Publisher Summary This chapter discusses mass spectrometry and computer technology in relation to gas-phase analytical methods based on gas chromatograph-mass spectrometer (GC-MS) instruments and gas chromatograph-mass spectrometer-computer (GC-MS-COM) analytical systems. The initial development of mass spectrometry was because of the physicists who were interested in atomic mass relationships, and all early studies were carried out with ionized gases of low molecular weight. The basic principle was: a stream of ions, projected into an electrostatic or magnetic field, follows a trajectory that depends upon the field strength and upon the mass/charge ratio of the ion. The function of the mass spectrometer is to separate ions in the gas phase, and to provide instrumental data that can be used to determine the mass/charge ratio and the relative abundance of each ion in the original mixture of ions generated in the source. The resolving power, mass range, and sensitivity of detection are of critical importance with respect to the purposes of the analytical applications. The scan speed is of lesser importance, but should be sufficiently fast for the applications under study.