Application of LC/MS to determine specific activity variation in a series of sulfonamide tracers from the [<sup>35</sup>S]methane sulfonate reagent

Schenk, David J.; Hesk, Dave; Marques, Rosemary; Helmy, Roy; Cheung, Patty

doi:10.1002/jlcr.2976

Cited by 2 publications

(3 citation statements)

References 7 publications

(12 reference statements)

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“…At the higher specific activities (~120 and 61 mCi/mol, entry 1, 2) the MS‐based values from using either the unlabeled or the [ 14 C 5 ] correction patterns were similar and were less than 10% different from the UV‐based values. This level of error is consistent with past investigations . With decreasing specific activity, there was a steadily increasing difference between the UV‐based specific activity values and both series of MS‐based values with the MS‐based values calculated from the unlabeled carbamazepine pattern always being the furthest from the UV‐based values.…”

Section: Resultssupporting

confidence: 91%

Determining the isotopic abundance of a labeled compound by mass spectrometry and how correcting for natural abundance distribution using analogous data from the unlabeled compound leads to a systematic error

Schenk

Lockley

Elmore

et al. 2016

J. Label Compd. Radiopharm

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When the isotopic abundance or specific activity of a labeled compound is determined by mass spectrometry (MS), it is necessary to correct the raw MS data to eliminate ion intensity contributions, which arise from the presence of heavy isotopes at natural abundance (e.g., a typical carbon compound contains ~1.1% (13) C per carbon atom). The most common approach is to employ a correction in which the mass-to-charge distribution of the corresponding unlabeled compound is used to subtract the natural abundance contributions from the raw mass-to-charge distribution pattern of the labeled compound. Following this correction, the residual intensities should be due to the presence of the newly introduced labeled atoms only. However, this will only be the case when the natural abundance mass isotopomer distribution of the unlabeled compound is the same as that of the labeled species. Although this may be a good approximation, it cannot be accurate in all cases. The implications of this approximation for the determination of isotopic abundance and specific activity have been examined in practice. Isotopically mixed stable-atom labeled valine batches were produced, and both these and [(14) C6 ]carbamazepine were analyzed by MS to determine the extent of the error introduced by the approach. Our studies revealed that significant errors are possible for small highly-labeled compounds, such as valine, under some circumstances. In the case with [(14) C6 ]carbamazepine, the errors introduced were minor but could be significant for (14) C-labeled compounds with particular isotopic distributions. This source of systematic error can be minimized, although not eliminated, by the selection of an appropriate isotopic correction pattern or by the use of a program that varies the natural abundance distribution throughout the correction.

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Section: Resultssupporting

confidence: 91%

Determining the isotopic abundance of a labeled compound by mass spectrometry and how correcting for natural abundance distribution using analogous data from the unlabeled compound leads to a systematic error

Schenk

Lockley

Elmore

et al. 2016

J. Label Compd. Radiopharm

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“…While the accuracy range of LC/MS SA determination has not been studied exhaustively, it has been demonstrated that the method error is roughly ~6–10%, and that the specific activity and elemental composition of the tracer has a significant effect on the measurement accuracy . The current study provides a similar error range (<10%) for the NMR SA method.…”

Section: Discussion Of Resultssupporting

confidence: 69%

“…Merck tritiated tracer, [ 3 H]compound A , and [1‐methyl, C 3 H 3 ]caffeine (ViTrax Co, Placentia CA, 19.8 Ci/mmol) were used as internal standards. Radiochemical purity (Agilent 1100 series HPLC, Agilent; Radiomatic 625TR, PerkinElmer), LC/MS‐derived specific activity (Agilent MSD) and radioactive solution count (TRI‐CARB 3100TR, PerkinElmer) for each were measured. Radio‐HPLC screening using six columns provided additional confidence that compound A 19 was radiochemically pure.…”

Section: Methodsmentioning

confidence: 99%

NMR‐based approach to the analysis of radiopharmaceuticals: radiochemical purity, specific activity, and radioactive concentration values by proton and tritium NMR spectroscopy

Schenk

Dormer

Hesk

et al. 2015

Labelled Comp Radiopharmac

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Compounds containing tritium are widely used across the drug discovery and development landscape. These materials are widely utilized because they can be efficiently synthesized and produced at high specific activity. Results from internally calibrated (3)H and (1)H nuclear magnetic resonance (NMR) spectroscopy suggests that at least in some cases, this calibrated approach could supplement or potentially replace radio-high-performance liquid chromatography for radiochemical purity, dilution and scintillation counting for the measurement of radioactivity per volume, and liquid chromatography/mass spectrometry analysis for the determination of specific activity. In summary, the NMR-derived values agreed with those from the standard approaches to within 1% to 9% for solution count and specific activity. Additionally, the NMR-derived values for radiochemical purity deviated by less than 5%. A benefit of this method is that these values may be calculated at the same time that (3)H NMR analysis provides the location and distribution of tritium atoms within the molecule. Presented and discussed here is the application of this method, advantages and disadvantages of the approach, and a rationale for utilizing internally calibrated (1)H and (3)H NMR spectroscopy for specific activity, radioactive concentration, and radiochemical purity whenever acquiring (3)H NMR for tritium location.

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Application of LC/MS to determine specific activity variation in a series of sulfonamide tracers from the [³⁵S]methane sulfonate reagent

Cited by 2 publications

References 7 publications

Determining the isotopic abundance of a labeled compound by mass spectrometry and how correcting for natural abundance distribution using analogous data from the unlabeled compound leads to a systematic error

Determining the isotopic abundance of a labeled compound by mass spectrometry and how correcting for natural abundance distribution using analogous data from the unlabeled compound leads to a systematic error

NMR‐based approach to the analysis of radiopharmaceuticals: radiochemical purity, specific activity, and radioactive concentration values by proton and tritium NMR spectroscopy

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Application of LC/MS to determine specific activity variation in a series of sulfonamide tracers from the [35S]methane sulfonate reagent

Cited by 2 publications

References 7 publications

Determining the isotopic abundance of a labeled compound by mass spectrometry and how correcting for natural abundance distribution using analogous data from the unlabeled compound leads to a systematic error

Determining the isotopic abundance of a labeled compound by mass spectrometry and how correcting for natural abundance distribution using analogous data from the unlabeled compound leads to a systematic error

NMR‐based approach to the analysis of radiopharmaceuticals: radiochemical purity, specific activity, and radioactive concentration values by proton and tritium NMR spectroscopy

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Application of LC/MS to determine specific activity variation in a series of sulfonamide tracers from the [³⁵S]methane sulfonate reagent