Ion specific detection of internal standards labeled with stable isotopes

Gaffney, Thomas E.; Hammar, Carl G.; Holmstedt, Bo; McMahon, Robert E.

doi:10.1021/ac60298a016

Cited by 122 publications

(36 citation statements)

References 6 publications

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“…Deuterium is the least expensive of the commonly used stable isotopes and is available in the widest variety of compounds; it is readily introduced into compounds by the usual synthetic methods. Gaffney et al (192) described the use of "internal standards" labeled with stable isotopes that correct for losses of the compound under study during the GLC treatment of the sample. With the mass spectrometer as the detector for the GLC effluent, chemical differences between the compound being determined and the internal standard are not necessary, because mass differences alone are sufficient to discriminate between the compound and the standard.…”

Section: Methods-stablementioning

confidence: 99%

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Studies with Deuterated Drugs

Blake

Crespi

Katz

1975

Journal of Pharmaceutical Sciences

113

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Section: Methods-stablementioning

confidence: 99%

“…Deuterated nortriptyline was used as an internal standard for unlabeled nortriptyline (192,194). In the synthesis of the labeled molecule, two deuterium atoms were introduced into the side chain as -CHCH2CD2NHCH3 (the M + 2 amu compound).…”

Section: Methods-stablementioning

confidence: 99%

Studies with Deuterated Drugs

Blake

Crespi

Katz

1975

Journal of Pharmaceutical Sciences

113

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“…23) in ylM amounts. Low tissue concentrations of the indoles and their lability (16,22,24) make assay by GC-SIM-MS4, with deuterated IAA as an internal standard, an attractive procedure. A number of procedures have been described using side chain d2-indoles as standards for assay of IAA and 5-hydroxy-IAA in plants and animals (1, 6, 10, 26).…”

mentioning

confidence: 99%

Synthesis of 4,5,6,7 and 2,4,5,6,7 Deuterium-labeled Indole-3-Acetic Acid for Use in Mass Spectrometric Assays

Magnus

Bandurski²,

Schulze³

1980

Plant Physiol.

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Syntheses are described for tetra and pentadeutero indole-3-acetic acid (IAA) labeled in positions 4, 5, 6, 7 or 2, 4, 5, 6, 7 of the indole moiety. Polydeuterated IAA is proposed as an internal standard for gas chromatographic-mass spectrometric analysis of IAA by selected ion monitoring. Nanogram amounts of IAA may be assayed by monitoring the base peak of IAA at m/z = 130 (134 for d4-IAA) and the molecular ion of the methyl ester of IAA at 189 (193 for d4-IAA). Deuterium in positions 4,5,6,and 7 and, to only a slightly lesser extent, that in position 2 of IAA is retained during alkali treatment, thus permitting use of these compounds as internal standards for assay of IAA released by alkaline hydrolysis of ester and amide conjugates. The use of polydeutero internal standards separates the standards from the "isotope cluster" caused by the normal abundance of heavy isotopes and also permits use of reduced mass resolution, thus leading to a 10-fold increase in sensitivity.Tetradeutero IAA was used as an internal standard for determining free plus ester IAA in alkaline hydrolysates of Zea mays, and showed exact agreement between estimates based on the molecular ion of the methyl ester and those based upon base peak. Application of the method to measuring free IAA in the upper and lower halves of geotropically stimulated Zea shoots showed 61 ± 4% of the free IAA to be on the lower side.Indolylic compounds, other than tryptophan, occur in plant (cf. 3, 4) and in animal tissue (cf. 23) in ylM amounts. Low tissue concentrations of the indoles and their lability (16,22,24) make assay by GC-SIM-MS4, with deuterated IAA as an internal standard, an attractive procedure. A number of procedures have been described using side chain d2-indoles as standards for assay of IAA and 5-hydroxy-IAA in plants and animals (1, 6, 10, 26). However, plants contain most of their IAA as ester or amide conjugates, conveniently assayed as free IAA, following hydrolysis of the esters by 1 N NaOH and the amide conjugates in 7 N NaOH (4). Alkaline hydrolysis precludes use of d2-IAA with deuterium in the side chain, since these deuterium are lost during base treatment. Deuterium in positions 4, 5, 6, and 7 is not exchanged with hydrogen during alkaline hydrolysis. Even deuterium in the 2 position is only slightly exchanged. ' To whom reprint requests should be directed.4Abbreviations: GC-SIM-MS, gas chromatography-selected ion monitoring-mass spectrometry; mp, melting point; NMR, nuclear magnetic resonance. synthesis for 4,5,6,7-d4-IAA and 2,4,5,6,7-d5-IAA and use of these compounds as internal standards.In addition to alkali stability, polydeuterated compounds provide additional advantages as internal standards for GC-SIM-MS. The ions generated by d4-and d5-IAA during MS are remote from the ions of IAA and, thus, the background caused by the normal abundances of heavy ions at I and 2 mass units above the IAA is eliminated. Further, providing sample purity is adequate, mass resolution may be broadened to ±+ amu (fat peak monitoring) y...

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“…The choice of IS often plays an important role in obtaining an accurate measurement by this technique. The use of stable-isotopically labeled IS has given good results [9][10][11]. Such stable isotopes, however, are not readily available due to their high price and complicated syntheses.…”

Section: Discussionmentioning

confidence: 99%

Forensic toxicologic analysis of methamphetamine and amphetamine in body materials by gas chromatography/mass spectrometry

1986

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Qualitative and quantitative analysis of methamphetamine and amphetamine in biologic materials was carried out by gas chromatography/mass spectrometry. A deuterium-labeled methamphetamine was employed as an internal standard with a detection limit of 50 pg and absolute stability and reproducibility. Blood was found to be the best material for estimation of the toxicity of the stimulant drug. It can be replaced by muscle which contains methamphetamine concentrations close to those of blood. The authors' classification of the toxic blood levels of methamphetamine from therapeutic to fatal doses was confirmed by additional data obtained from new case studies.

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Ion specific detection of internal standards labeled with stable isotopes

Cited by 122 publications

References 6 publications

Studies with Deuterated Drugs

Studies with Deuterated Drugs

Synthesis of 4,5,6,7 and 2,4,5,6,7 Deuterium-labeled Indole-3-Acetic Acid for Use in Mass Spectrometric Assays

Forensic toxicologic analysis of methamphetamine and amphetamine in body materials by gas chromatography/mass spectrometry

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