Deiodination of iodinated aromatic compounds with electrospray ionization mass spectrometry

Adeno-associated viruses (AAVs) are non-enveloped viruses which have become popular gene transfer vectors to deliver DNA to target cells in clinical gene therapy. Iodixanolbased density gradient is one of the widely used purification methods for serotypeindependent AAV. However, residual iodixanol in AAV could be a safety concern, and further purification to remove this process-related impurity is typically needed. An analytical assay with high sensitivity is essential for the detection of residual iodixanol to ensure the safety of AAV products. We developed a liquid chromatography-mass spectrometry (LC-MS) method with the limit of quantification (LOQ) of 0.01 μg/mL for residual iodixanol measurement in AAV. The method also demonstrated linearity over four orders of magnitude which allows quantifying a high iodixanol concentration in in-process samples with excellent recovery and accuracy. In addition, we further explored a highly efficient purification method for removal of the residual iodixanol, to minimize the safety concern from iodixanol as a process impurity.

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“…No deiodinated species was observed for both iodixanol and iohexol within the conditions evaluated in this study. 17 …”

Section: Resultsmentioning

confidence: 99%

Development and Application of a Liquid Chromatography-Mass Spectrometry Method for Residual Iodixanol Quantification in AAV-Based Gene Therapy Product Development

Katz²,

Chen

et al. 2022

Human Gene Therapy

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“…The NL-peaks were also detected in standard solution. Hvattum et.al . investigated this behavior and found that formic acid induces deiodination in the ESI capillary of the MS instrument.…”

Section: Resultsmentioning

confidence: 99%

“…Hvattum et.al. 21 investigated this behavior and found that formic acid induces deiodination in the ESI capillary of the MS instrument. The same was observed for IOX-TP695-A and B, where (apart from the two TPs) a neutral loss of iodine from IOX shows a peak at 2.89 min which is the same retention time as IOX.…”

Section: )mentioning

confidence: 99%

LC-HRMS Suspect Screening for Detection-Based Prioritization of Iodinated Contrast Media Photodegradates in Surface Waters

Žonja

Delgado

Pérez

et al. 2015

Environ. Sci. Technol.

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The objective of the study was to demonstrate the applicability of suspect screening for the detection of six iodinated contrast media (ICM) and their phototransformation products (TPs) in surface waters. First, a photodegradation study of ICM in surface water using a sunlight lab-scale simulator was performed. By means of a guided differential sample analysis, the exact masses of the molecular ions and the retention times of TPs were identified. Positive findings were filtered manually generating a suspect list of 108 photoproducts. Following a generic solid-phase extraction of surface water samples, LC-HRMS was used to screen for the presence of the compounds previously detected in the photodegradation samples. On the basis of detection frequencies (>50% of the samples), 11 TPs were prioritized and their structures elucidated by HRMS and NMR. In the real surface water samples, median concentration of parent compounds was 110 ng/L reaching up to 6 μg/L for iomeprol, while TPs were found at median concentration of 8 ng/L, reaching up to 0.4 μg/L for iomeprol TP651-B. In summary, the proposed screening approach facilitates the evaluation of the degradation of polar compounds at a real scale with a fast detection of TPs without prior availability of the standards.

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“…Finally, dehalogenation of iodinated aromatic compounds when performing HPLC-ES-MS/MS measurement in both +ve and Àve modes has been reported by Hvattum et al 120 The iodinated aromatic compounds were analyzed on a YMC-Pack ODS AM column (150 Â 4.6 mm, 5 mm) using gradient elution from 100% water to 50% acetonitrile. In the rst 118 iodine speciation in human urine by RP HPLC-ICP-MS is described.…”

Section: Halogensmentioning

confidence: 98%

“…It was found that I was associated with alkaline proteins with RMM of 10, 20, 28, 40 and 110 kDa in the alkaline (pH 8.0-9.0) isoelectric point (pI) range. Finally, dehalogenation of iodinated aromatic compounds when performing HPLC-ES-MS/MS measurement in both +ve and Àve modes has been reported by Hvattum et al 120 The iodinated aromatic compounds were analyzed on a YMC-Pack ODS AM column (150 Â 4.6 mm, 5 mm) using gradient elution from 100% water to 50% acetonitrile. The effect of mobile phase additive on the deiodination reaction was evaluated by using formic acid, acetic acid, triuoroacetic acid, ammonium formate and ammonium acetate as modiers.…”

Section: Halogensmentioning

confidence: 98%

Atomic Spectrometry Update: review of advances in elemental speciation

Harrington

Clough

Hill

et al. 2015

J. Anal. At. Spectrom.

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Deiodination of iodinated aromatic compounds with electrospray ionization mass spectrometry

Abstract: Care should be taken when using formic acid as a mobile phase additive in LC/MS analyses of iodinated aromatic compounds, since the interpretation of the mass spectra might be influenced by potential dehalogenation reactions taking place in the ESI capillary.

Cited by 4 publications

References 29 publications

Development and Application of a Liquid Chromatography-Mass Spectrometry Method for Residual Iodixanol Quantification in AAV-Based Gene Therapy Product Development

Development and Application of a Liquid Chromatography-Mass Spectrometry Method for Residual Iodixanol Quantification in AAV-Based Gene Therapy Product Development

LC-HRMS Suspect Screening for Detection-Based Prioritization of Iodinated Contrast Media Photodegradates in Surface Waters

Atomic Spectrometry Update: review of advances in elemental speciation

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