Determination of stimulants using gas chromatography/high-resolution time-of-flight mass spectrometry and a soft ionization source.

RATIONALE: The aim of this study was to investigate the mass spectral fragmentation of a small set of stimulants in a high-resolution time-of-flight mass spectrometer equipped with a soft ionization source using vacuum ultraviolet (VUV) photons emitted from different plasma gases. It was postulated that the use of a plasma gas such as Xe, which emits photons at a lower energy than Kr or Ar, would lead to softer ionization of the test compounds, and thus to less fragmentation. METHODS: A set of nine stimulants: cocaine, codeine, nicotine, methadone, phenmetrazine, pentylenetetrazole, niketamide, fencamfamine, and caffeine, was analyzed by gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) in positive ion mode with this soft ionization source, using either Xe, Kr, or Ar as plasma gases. Working solutions of the test compounds at 0.1 to 100 ng/µL were used to establish instrument sensitivity and linearity. RESULTS: All test compounds, except methadone and pentylenetetrazole, exhibited strong molecular ions and no fragmentation with Xe-microplasma photoionization (MPPI). Methadone exhibited significant fragmentation not only with Xe, but also with Kr and Ar, and pentylenetetrazole could not be ionized with Xe, probably because its ionization energy is above 8.44 eV. The Kr- and Ar-MPPI mass spectra of the test compounds showed that the relative intensity of the molecular ion decreased as the photon energy increased. CONCLUSIONS: When coupled to a TOF mass spectrometer this soft ionization source has demonstrated signal-to-noise (S/N) ratios from 7 to 730 at 100 pg per injection (depending on the compound), and a dynamic range of three orders of magnitude (100 pg to 100 ng) for some of the test compounds.

Spectrophotometric determination of nikethamide by charge--transfer complexation with chloranilic acid.

A Spectrophotometric method is described for assay of nikethamide which was based on charge transfer complexation between it and chloranilic acid. They form a complex with stoichiometric ratio of 1:1 and showed l-max at 535 nm. Maximum complexation occurred 30 min after mixing the reactants and was stable for 12 hr. The molar absorptivity, association constant and free energy for the complex were 1.05 x 1.0(2), 4.40 x 10(-2) litre mole-1 and 1819.02 kcal respectively. Conformity to Beer's Law was within the concentration range of 1-2.5 x 10(-4), which enabled the assay of dosage forms of the drug at microquantities.

[Studies on the reaction of plastics with drug solutions. Part 3: The effects of the pigment content and of the colouring techniques (author's transl)]. / Untersuchungen zum Verhalten von Kunststoffen gegenüber Arzneistofflösungen. 3. Mitteilung: Einfluss des Pigmentgehaltes und der Einfärbetechnologie. 48. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältnissen für flüssige Arzneizubereitungen.

The effects of the pigment content and of the colouring technique on stress-cracking are demonstrated by the example of the low-density polyethylene Mirathen A 13 EA. A 99% aqueous nikethamide solution was used as the drug solution. The sorption increased as the pigment content increased, which testifies to a relationship between the amount of the medium sorbed and the pharmaceutical ageing.

[Studies on the reaction of plastics with drug solutions. Part 2: Nikethamide (author's transl)]. / Untersuchungen zum Verhalten von Kunststoffen gegenüber Arzneistofflösungen. 2. Mitteilung: Nicethamid. 46. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältnissen für flüssige Arzneizubereitungen.

The authors describe the effects of nikethamide solutions of varying concentrations on natural-coloured and red-coloured low-density polyethylene. For this purpose, they analyse the findings from stress-crack studies performed by means of a test method previously described [6,7]. The results obtained lead to a new interpretation of pharmaceutical ageing under the given conditions.

Gas-liquid chromatographic determination of nikethamide in injectable preparations.

A gas-liquid chromatographic (GLC) method, using a 4% XE-60 on 80-100 mesh Gas-Chrom Q column, a flame ionization detector, and anthracene as the internal standard, has been developed for the direct determination of nikethamide. Eight collaborators analyzed 4 samples, using methanol as the solvent; the coefficients of variation obtained ranged from 1.19 to 3.20%. In a limited study with acetone as the solvent, the coefficients of variation ranged from 0.59 to 1.96%. The GLC method with acetone as a solvent has been adopted as official first action.