PMID- 16715365
OWN - NLM
STAT- MEDLINE
DCOM- 20070213
LR  - 20181113
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 23
IP  - 6
DP  - 2006 Jun
TI  - FTIR and nDSC as analytical tools for high-concentration protein formulations.
PG  - 1350-63
AB  - PURPOSE: The aim of the study is to evaluate Fourier-transform infrared 
      spectroscopy (FTIR) as an analytical tool for high-concentrated protein 
      formulations. METHODS: FTIR is used to determine the melting temperature (T(m 
      (FTIR))) of various proteins, such as bovine serum albumin (BSA), immunoglobulin 
      (IgG1), beta-lactoglobulin (beta-LG), and lysozyme (HEWL), at different protein 
      concentrations (5-100 mg/mL), where four data interpretation methods are 
      discussed. The obtained T(m (FTIR)) values are further compared to the T(m) 
      measured by the nanodifferential scanning calorimetry (nDSC) technique. RESULTS: 
      The T(m (FTIR)) values of IgG1 and beta-LG showed strong consistency and 
      corresponded to the nDSC results irrespective of the method of data 
      interpretation and the protein concentration applied. In contrast, the T(m 
      (FTIR)) of BSA and HEWL is characterized by significant deviations. Only the 
      midpoint of the second-derivative intensity-temperature curve of the 
      intermolecular beta-sheet mode measured at a concentration of 100 mg/mL is 
      consistent with the nDSC results. CONCLUSIONS: Determination of a T(m (FTIR)) is 
      feasible by the midpoint of the intensity-temperature plot of the arising 
      intermolecular beta-sheet band. More significant results are obtained for 
      proteins, which are predominantly composed of intramolecular beta-sheet elements 
      as well as at higher protein concentrations. A further study was started to 
      assess the predictability of long-term protein stability by T(m (FTIR)).
FAU - Matheus, Susanne
AU  - Matheus S
AD  - Merck KGaA, Global Pharmaceutical Development, Darmstadt, Germany.
FAU - Friess, Wolfgang
AU  - Friess W
FAU - Mahler, Hanns-Christian
AU  - Mahler HC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20060526
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lactoglobulins)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - EC 3.2.1.17 (Muramidase)
SB  - IM
MH  - *Calorimetry, Differential Scanning
MH  - Chemistry, Pharmaceutical
MH  - Enzyme Stability
MH  - Immunoglobulin G/*chemistry
MH  - Lactoglobulins/*chemistry
MH  - Muramidase/*chemistry
MH  - *Nanotechnology
MH  - Protein Denaturation
MH  - Protein Folding
MH  - Protein Structure, Secondary
MH  - Serum Albumin, Bovine/*chemistry
MH  - *Spectroscopy, Fourier Transform Infrared
MH  - Thermodynamics
MH  - Transition Temperature
EDAT- 2006/05/23 09:00
MHDA- 2007/02/14 09:00
CRDT- 2006/05/23 09:00
PHST- 2005/11/10 00:00 [received]
PHST- 2006/01/27 00:00 [accepted]
PHST- 2006/05/23 09:00 [pubmed]
PHST- 2007/02/14 09:00 [medline]
PHST- 2006/05/23 09:00 [entrez]
AID - 10.1007/s11095-006-0142-8 [doi]
PST - ppublish
SO  - Pharm Res. 2006 Jun;23(6):1350-63. doi: 10.1007/s11095-006-0142-8. Epub 2006 May 
      26.