Analysis of Insulin Allostery in Solution and Solid State With FTIR

Maltesen, Morten Jonas; Bjerregaard, Simon; Hovgaard, Lars; Havelund, Svend; Weert, Marco van de

doi:10.1002/jps.21736

Cited by 13 publications

(13 citation statements)

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“…The reference method used to analyse the phenol concentration of dehydrated samples was RP-UPLC on a Waters Acquity system (Waters Corporation, Milford, MA, USA) (12). The spray-dried or freeze-dried samples were reconstituted in water to a total solid content of approximately 2.5 mg/mL and 2 μL was injected on the C18 column (Acquity UPLC BEH C18, 1.7 μm, 2.1×50 mm) kept at 30°C.…”

Section: Reversed Phase Ultra Performance Liquid Chromatographymentioning

confidence: 99%

“…The second derivative transformation of the spectra reverses the sign of the spectra and a peak in the loading corresponds to a decrease in the original spectra. Part of the increase in α-helix content is correlated with the phenol/insulin ratio as an increase in ratio results in an increase in the α-helix content of the insulin hexamer (12). However, some of the variations cannot be explained by the insulin/phenol ratio and is credited to unknown variations in the dried powders.…”

Section: Multivariate Analyses Of Ftir Spectramentioning

confidence: 99%

“…Recently, we have expanded the allosteric concepts of insulin to solid state formulations (12). We showed that it was possible to maintain the increase in the α-helix content of insulin in the presence of phenol after drying.…”

Section: Introductionmentioning

confidence: 99%

“…An important part of that study was to correlate the structural changes of the insulin hexamer with the residual amount of phenol present in the formulation after drying. The residual phenol content in the dried samples was evaluated by reverse phase (RP) ultra performance liquid chromatography (UPLC) (12). The advantages of the UPLC methods are high resolution, high sensitivity and a high level of robustness, including reproducibility and accuracy (13).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, online analysis of phenol content during dehydration would provide fast and real time monitoring of an important CQA throughout the dehydration process. The control method used is based on a reverse phase liquid chromatography method where the samples are reconstituted in order to measure the phenol content (12). The two spectroscopic methods evaluated, FTIR and NIR, yield similar type of information, but they have different advantages and drawbacks.…”

Section: Introductionmentioning

confidence: 99%

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Multivariate Analysis of Phenol in Freeze-Dried and Spray-Dried Insulin Formulations by NIR and FTIR

et al. 2011

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Dehydration is a commonly used method to stabilise protein formulations. Upon dehydration, there is a significant risk the composition of the formulation will change especially if the protein formulation contains volatile compounds. Phenol is often used as excipient in insulin formulations, stabilising the insulin hexamer by changing the secondary structure. We have previously shown that it is possible to maintain this structural change after drying. The aim of this study was to evaluate the residual phenol content in spray-dried and freeze-dried insulin formulations by Fourier transform infrared (FTIR) spectroscopy and near infrared (NIR) spectroscopy using multivariate data analysis. A principal component analysis (PCA) and partial least squares (PLS) projections were used to analyse spectral data. After drying, there was a difference between the two drying methods in the phenol/insulin ratio and the water content of the dried samples. The spray-dried samples contained more water and less phenol compared with the freeze-dried samples. For the FTIR spectra, the best model used one PLS component to describe the phenol/insulin ratio in the powders, and was based on the second derivative pre-treated spectra in the 850-650 cm −1 region. The best PLS model based on the NIR spectra utilised three PLS components to describe the phenol/insulin ratio and was based on the standard normal variate transformed spectra in the 6,200-5,800 cm −1 region. The root mean square error of cross validation was 0.69% and 0.60% (w/w) for the models based on the FTIR and NIR spectra, respectively. In general, both methods were suitable for phenol quantification in dried phenol/insulin samples.

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Section: Reversed Phase Ultra Performance Liquid Chromatographymentioning

confidence: 99%

Section: Multivariate Analyses Of Ftir Spectramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multivariate Analysis of Phenol in Freeze-Dried and Spray-Dried Insulin Formulations by NIR and FTIR

et al. 2011

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Electronic Circular Dichroism Spectroscopy

Zsila¹

2010

Pharmaceutical Sciences Encyclopedia

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Electronic circular dichroism (ECD or CD) is the manifestation of the important property of chiral compounds to absorb left and right circularly polarized light to different extents. Electronic circular dichroism (CD) spectroscopy technique has been used for investigation of chiral drugs and other pharmaceutical preparations. This article focuses on basic features, instrumentation, advantages, limitations, and practical applications of electronic circular dichroism (CD) spectroscopy in pharmaceutical sciences.

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