Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy

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Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. / Schou-Pedersen, Anne Marie V; Cornett, Claus; Nyberg, Nils; Østergaard, Jesper; Hansen, Steen Honoré.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 107C, 25.03.2015, p. 333-340.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Schou-Pedersen, AMV, Cornett, C, Nyberg, N, Østergaard, J & Hansen, SH 2015, 'Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy', Journal of Pharmaceutical and Biomedical Analysis, vol. 107C, pp. 333-340. https://doi.org/10.1016/j.jpba.2015.01.022

APA

Schou-Pedersen, A. M. V., Cornett, C., Nyberg, N., Østergaard, J., & Hansen, S. H. (2015). Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Journal of Pharmaceutical and Biomedical Analysis, 107C, 333-340. https://doi.org/10.1016/j.jpba.2015.01.022

Vancouver

Schou-Pedersen AMV, Cornett C, Nyberg N, Østergaard J, Hansen SH. Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Journal of Pharmaceutical and Biomedical Analysis. 2015 Mar 25;107C:333-340. https://doi.org/10.1016/j.jpba.2015.01.022

Author

Schou-Pedersen, Anne Marie V ; Cornett, Claus ; Nyberg, Nils ; Østergaard, Jesper ; Hansen, Steen Honoré. / Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. In: Journal of Pharmaceutical and Biomedical Analysis. 2015 ; Vol. 107C. pp. 333-340.

Bibtex

@article{61816d10e36c47408350fe6c1bc01556,
title = "Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy",
abstract = "Concentrated solutions containing 6-aminocaproic acid and the excipients citric acid and sorbitol have been studied at temperatures of 50 °C, 60 °C, 70 °C and 80 °C as well as at 20 °C. It has previously been reported that the commonly employed citric acid is a reactive excipient, and it is therefore important to thoroughly investigate a possible reaction between 6-aminocaproic acid and citric acid. The current study revealed the formation of 3-hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid between 6-aminocaproic acid and citric acid by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance spectroscopy (NMR). Less than 0.03{\%} of 6-aminocaproic acid was converted to 3-hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid after 30 days of storage at 80 °C. Degradation products of 6-aminocaproic acid were also observed after storage at the applied temperatures, e.g., dimer, trimer and cyclized 6-aminocaproic acid, i.e., caprolactam. No reaction products between d-sorbitol and 6-aminocaproic acid could be observed. 3-Hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid, dimer and caprolactam were also observed after storage at 20 °C for 3 months. The findings imply that an oral solution of 6-aminocaproic acid is relatively stable at 20 °C at the pH values 4.00 and 5.00 as suggested in the USP for oral formulations. Compliance with the ICH guideline Q3B is expected.",
author = "Schou-Pedersen, {Anne Marie V} and Claus Cornett and Nils Nyberg and Jesper {\O}stergaard and Hansen, {Steen Honor{\'e}}",
note = "Copyright {\circledC} 2015 Elsevier B.V. All rights reserved.",
year = "2015",
month = "3",
day = "25",
doi = "10.1016/j.jpba.2015.01.022",
language = "English",
volume = "107C",
pages = "333--340",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Structure elucidation and quantification of impurities formed between 6-aminocaproic acid and the excipients citric acid and sorbitol in an oral solution using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy

AU - Schou-Pedersen, Anne Marie V

AU - Cornett, Claus

AU - Nyberg, Nils

AU - Østergaard, Jesper

AU - Hansen, Steen Honoré

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2015/3/25

Y1 - 2015/3/25

N2 - Concentrated solutions containing 6-aminocaproic acid and the excipients citric acid and sorbitol have been studied at temperatures of 50 °C, 60 °C, 70 °C and 80 °C as well as at 20 °C. It has previously been reported that the commonly employed citric acid is a reactive excipient, and it is therefore important to thoroughly investigate a possible reaction between 6-aminocaproic acid and citric acid. The current study revealed the formation of 3-hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid between 6-aminocaproic acid and citric acid by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance spectroscopy (NMR). Less than 0.03% of 6-aminocaproic acid was converted to 3-hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid after 30 days of storage at 80 °C. Degradation products of 6-aminocaproic acid were also observed after storage at the applied temperatures, e.g., dimer, trimer and cyclized 6-aminocaproic acid, i.e., caprolactam. No reaction products between d-sorbitol and 6-aminocaproic acid could be observed. 3-Hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid, dimer and caprolactam were also observed after storage at 20 °C for 3 months. The findings imply that an oral solution of 6-aminocaproic acid is relatively stable at 20 °C at the pH values 4.00 and 5.00 as suggested in the USP for oral formulations. Compliance with the ICH guideline Q3B is expected.

AB - Concentrated solutions containing 6-aminocaproic acid and the excipients citric acid and sorbitol have been studied at temperatures of 50 °C, 60 °C, 70 °C and 80 °C as well as at 20 °C. It has previously been reported that the commonly employed citric acid is a reactive excipient, and it is therefore important to thoroughly investigate a possible reaction between 6-aminocaproic acid and citric acid. The current study revealed the formation of 3-hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid between 6-aminocaproic acid and citric acid by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance spectroscopy (NMR). Less than 0.03% of 6-aminocaproic acid was converted to 3-hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid after 30 days of storage at 80 °C. Degradation products of 6-aminocaproic acid were also observed after storage at the applied temperatures, e.g., dimer, trimer and cyclized 6-aminocaproic acid, i.e., caprolactam. No reaction products between d-sorbitol and 6-aminocaproic acid could be observed. 3-Hydroxy-3,4-dicarboxy-butanamide-N-hexanoic acid, dimer and caprolactam were also observed after storage at 20 °C for 3 months. The findings imply that an oral solution of 6-aminocaproic acid is relatively stable at 20 °C at the pH values 4.00 and 5.00 as suggested in the USP for oral formulations. Compliance with the ICH guideline Q3B is expected.

U2 - 10.1016/j.jpba.2015.01.022

DO - 10.1016/j.jpba.2015.01.022

M3 - Journal article

C2 - 25645337

VL - 107C

SP - 333

EP - 340

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -

ID: 131693632