Time-Dependent Changes of Oxytocin Using 1H-NMR Coupled with Multivariate Analysis: a New Approach for Quality Evaluation of Protein/Peptide Biologic Drugs

Ohno, Akiko; Kawasaki, Nana; Fukuhara, Kiyoshi; Okuda, Haruhiro; Yamaguchi, Teruhide

doi:10.1248/cpb.57.1396

Cited by 8 publications

(9 citation statements)

References 15 publications

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“…170 A method developed by Ohno et al combines 1 H NMR and principal component analysis (PCA) to obtain the quality evaluation of biopharmaceuticals, with regard to their quality, consistency, and differences in protein modification patterns. 171 The feasibility of the method was assessed by collecting three 1 H NMR spectra of oxytocin ( 51 ) at days 0, 7 and 14. Although the three spectra of 51 seemed similar by simple visual inspection, time-dependent differences among the three spectra were clearly distinguished by a PCA score plot.…”

Section: Qhnmr For the Assessment Of Residual Complexity And Puritymentioning

confidence: 99%

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Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update

et al. 2012

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Covering the literature from mid-2004 until the end of 2011, this review continues a previous literature overview on quantitative 1 H NMR (qHNMR) methodology and its applications in the analysis of natural products. Among the foremost advantages of qHNMR is its accurate function with external calibration, the lack of any requirement for identical reference materials, a high precision and accuracy when properly validated, and an ability to quantitate multiple analytes simultaneously. As a result of the inclusion of over 170 new references, this updated review summarizes a wealth of detailed experiential evidence and newly developed methodology that supports qHNMR as a valuable and unbiased analytical tool for natural product and other areas of research.

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Section: Qhnmr For the Assessment Of Residual Complexity And Puritymentioning

confidence: 99%

“…The results demonstrate that PCA in combination with 1 H NMR is a powerful tool for the evaluation of dynamic RC, especially when differences between spectra cannot be determined visually. 171 …”

Section: Qhnmr For the Assessment Of Residual Complexity And Puritymentioning

confidence: 99%

Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update

et al. 2012

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“…1,2) Currently, multivariate statistical methods, which combine various analytical methods, have been widely used to evaluate the quality of drugs and foods, quantitatively or qualitatively, in addition to enabling predictions of drug metabolism, and toxicity. [3][4][5][6][7][8][9][10] Compared with small-molecule drugs, polypeptides are heterogeneous and are more complex in their makeup for a number of possible reasons including mutations in the amino acid sequence of the protein, different posttranslational modifications, or by being a mixture of molecules with different terminal structures due to degradation by contaminating proteases.…”

Section: H-nmrmentioning

confidence: 99%

“…In our recent study, it was reported that peak changes in the determination of characteristic spectral changes associated with time-dependent alterations of oxytocin (OXT) were also observed in the PCA loading plot. 8,12) Thus, the possibility of evaluating slight differences in the quality of a polypeptide was demonstrated.…”

Section: H-nmrmentioning

confidence: 99%

A New Approach to Characterization of Insulin Derived from Different Species Using 1H-NMR Coupled with Multivariate Analysis

Ohno¹,

Kawanishi²,

Okuda³

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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Most of the active components of polypeptides have a complex molecular structure, large molecular size. Such components may also be structurally heterogeneous. Therefore, development of a method that can confirm the consistency of polypeptides amino-acid sequences for product characterization is desirable. In general, it is extremely difficult to distinguish differences of a few amino acid residues in the 1 H-NMR spectrum of polypeptides with molecular weights greater than several thousand. However, we have been able to distinguish between three insulin species differing in one to three amino acid residues using a combination of multivariate statistics and 1 H-NMR spectra. These results demonstrate that this methodology could be useful for characterization of polypeptides.

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“…Because of the complex nature of natural extracts, direct in situ NMR monitoring of dynamic changes in composition represents a significant challenge that has been rarely addressed in the current scientific literature. As pointed out by Pauli et al , stability studies, reaction mechanisms, and kinetic studies involving natural products are essentially lacking in the literature up to 2004 with only three publications in the period of 2005–2011 . Furthermore, no results have so far been reported on the thermodynamic basis of the effects of solvent and temperature in mixture analysis of natural products.…”

Section: Introductionmentioning

confidence: 99%

Dynamic changes in composition of extracts of natural products as monitored by in situ NMR

Charisiadis

Tsiafoulis

Tzakos

et al. 2014

Magnetic Reson in Chemistry

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The direct in situ NMR observation and quantification, based on the aldehyde -CH chemical shift region, of the inter-conversion of secoiridoid derivatives due to temperature and solvent effects is demonstrated in complex extracts of natural products without prior isolation of the individual components. The equilibrium between the aldehyde hydrate form and the dialdehyde form of the oleuropein aglycon of an olive leaf aqueous extract in D(2)O was shown to be temperature dependent. The resulting thermodynamic values of the Van't Hoff plot with ΔH(o) = -26.34 ± 1.00 kJ mol(-1) and TΔS° (298 K) = -24.70 ± 1.00 kJ mol(-1) demonstrate a significant entropy term which nearly compensates the effect of enthalpy at room temperature. The equilibrium between the two diastereomeric hemiacetal forms and the dialdehyde form of the oleuropein 6-O-β-d-glucopyranoside aglycon of an olive leaf aqueous extract in CD(3) OD was also shown to be strongly temperature dependent again because of the significant entropy term (TΔS° (298 K) = -26.50 ± 1.39 kJ mol(-1)) compared with that of the enthalpy term (ΔH(o) = -36.64 ± 1.46 kJ mol(-1)). This is the first demonstration of the significant role of the entropy parameter in determining the equilibrium of chemical transformations in complex mixtures of natural products due to solvent and temperature effects.

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Time-Dependent Changes of Oxytocin Using 1H-NMR Coupled with Multivariate Analysis: a New Approach for Quality Evaluation of Protein/Peptide Biologic Drugs

Cited by 8 publications

References 15 publications

Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update

Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update

A New Approach to Characterization of Insulin Derived from Different Species Using 1H-NMR Coupled with Multivariate Analysis

Dynamic changes in composition of extracts of natural products as monitored by in situ NMR

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Time-Dependent Changes of Oxytocin Using 1H-NMR Coupled with Multivariate Analysis: a New Approach for Quality Evaluation of Protein/Peptide Biologic Drugs

Cited by 8 publications

References 15 publications

Quantitative 1H NMR. Development and Potential of an Analytical Method: An Update

Quantitative 1H NMR. Development and Potential of an Analytical Method: An Update

A New Approach to Characterization of Insulin Derived from Different Species Using 1H-NMR Coupled with Multivariate Analysis

Dynamic changes in composition of extracts of natural products as monitored by in situ NMR

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Product

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Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update

Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update