Development of an automated system for preparation of liquid scintillation counting samples for radiolabeled pharmaceuticals

Marques, Rosemary; Bernardoni, Frank; Pollack, Scott; Helmy, Roy

doi:10.1002/jlcr.3156

Cited by 4 publications

(2 citation statements)

References 8 publications

(4 reference statements)

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“…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: 51%

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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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Section: Methodsmentioning

confidence: 51%

“…Duplicate radio‐HPLC and LC/MS injections were performed for radiochemical purity and LC/MS SA measurements. The radioactive concentrations were determined using duplicate initial dilutions followed by duplicate sampling and scintillation counting of each initial dilution. All tracers were received and stored as dilute ethanol solutions.…”

Section: Methodsmentioning

confidence: 51%

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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Mass Spectrometric and Functional Aspects of Drug–Protein Conjugation

Tailor

Waddington

Meng

et al. 2016

Chem. Res. Toxicol.

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The covalent binding of drugs (metabolites) to proteins to form drug-protein adducts can have an adverse effect on the body. These adducts are thought to be responsible for idiosyncratic drug reactions including severe drug hypersensitivity reactions. Major advances in proteomics technology have allowed for the identification and quantification of target proteins for certain drugs. Human serum albumin (HSA) and Hb have been identified as accessible targets and potential biomarkers for drug-protein adducts formation, for numerous drugs (metabolites) including β-lactam antibiotics, reactive drug metabolites such as quinone imines (acetaminophen) and acyl glucuronides (diclofenac), and covalent inhibitors (neratinib). For example, MS/MS analysis of plasma samples from patients taking flucloxacillin revealed that flucloxacillin and its 5-hydroxymethyl metabolite formed covalent adducts with lysine residues on albumin via opening of the β-lactam ring. Other proteins such as P450 and keratin are also potential targets for covalent binding. However, for most drugs, the properties of these target proteins including their location, their quantity, the timing of conjugate generation, and their biological function are not well understood. In this review, currently available proteomic technologies including MS/MS analysis to identify antigens, precise location of modifications, and the immunological consequence of hapten-protein complex are illustrated. Moving forward, identification of the nature of the antigenic determinants that trigger immune responses to drug-protein adducts will increase our ability to predict idiosyncratic toxicity for a given compound.

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Drug hypersensitivity reactions: review of the state of the science for prediction and diagnosis

Pallardy,

Bechara,

Whritenour

et al. 2024

Toxicological Sciences

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Drug hypersensitivity reactions (DHRs) are a type of adverse drug reaction that can occur with different classes of drugs and affect multiple organ systems and patient populations. DHRs can be classified as allergic or non-allergic based on the cellular mechanisms involved. Whereas non-allergic reactions rely mainly on the innate immune system, allergic reactions involve the generation of an adaptive immune response. Consequently, drug allergies are DHRs for which an immunological mechanism, with antibody and/or T cell, is demonstrated. Despite decades of research, methods to predict the potential for a new chemical entity to cause DHRs or to correctly attribute DHRs to a specific mechanism and a specific molecule are not well-established. This review will focus on allergic reactions induced by systemically administered low molecular weight (LMW) drugs with an emphasis on drug- and patient-specific factors that could influence the development of DHRs. Strategies for predicting and diagnosing DHRs, including potential tools based on the current state of the science, will also be discussed.

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Development of an automated system for preparation of liquid scintillation counting samples for radiolabeled pharmaceuticals

Cited by 4 publications

References 8 publications

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

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

Mass Spectrometric and Functional Aspects of Drug–Protein Conjugation

Drug hypersensitivity reactions: review of the state of the science for prediction and diagnosis

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