PMID- 22497462
OWN - NLM
STAT- MEDLINE
DCOM- 20120919
LR  - 20120515
IS  - 1520-6882 (Electronic)
IS  - 0003-2700 (Linking)
VI  - 84
IP  - 10
DP  - 2012 May 15
TI  - Analytical characterization of an orally-delivered peptide pharmaceutical 
      product.
PG  - 4357-72
LID - 10.1021/ac203478r [doi]
AB  - The characterization of orally-delivered peptide pharmaceuticals presents several 
      challenges to analytical methods in comparison to characterization of 
      conventional small-molecule drugs. These challenges include the analysis and 
      characterization of difficult-to-separate impurities, secondary structure, the 
      amorphous solid-state form, and the integrity of enteric-coated drug delivery 
      systems. This work presents the multidisciplinary analytical characterization of 
      a parathyroid hormone (PTH) peptide active pharmaceutical ingredient (API) and an 
      oral formulation of this API within enteric-coated sucrose spheres. The analysis 
      of impurities and degradation products in API and formulated drug product was 
      facilitated by the development of an ultrahigh-performance liquid chromatography 
      (UHPLC) method for analysis by high-resolution mass spectrometry (MS). The use of 
      UHPLC allowed for additional resolution needed to detect impurities and 
      degradation products of interest. The secondary structure was probed using a 
      combination of solution-state NMR, infrared, and circular dichroism spectroscopic 
      methods. Solid-state NMR is used to detect amorphous API in a nondestructive 
      manner directly within the coated sucrose sphere formulation. Fluorescence and 
      Raman microscopy were used in conjunction with Raman mapping to show enteric 
      coating integrity and observe the distribution of API beneath the enteric-coating 
      on the sucrose spheres. The methods are combined in a multidisciplinary approach 
      to characterize the quality of the enteric-coated peptide product.
FAU - Kelley, Wayne P
AU  - Kelley WP
AD  - Biopharmaceutical R&D, GlaxoSmithKline llc., King of Prussia, Pennsylvania 19406, 
      United States.
FAU - Chen, Shujun
AU  - Chen S
FAU - Floyd, Philip D
AU  - Floyd PD
FAU - Hu, Ping
AU  - Hu P
FAU - Kapsi, Shiva G
AU  - Kapsi SG
FAU - Kord, Alireza S
AU  - Kord AS
FAU - Sun, Mingjiang
AU  - Sun M
FAU - Vogt, Frederick G
AU  - Vogt FG
LA  - eng
PT  - Journal Article
DEP - 20120427
PL  - United States
TA  - Anal Chem
JT  - Analytical chemistry
JID - 0370536
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Peptides)
RN  - 0 (Recombinant Proteins)
RN  - 57-50-1 (Sucrose)
SB  - IM
MH  - Administration, Oral
MH  - Amino Acid Sequence
MH  - *Chromatography, High Pressure Liquid
MH  - *Drug Compounding
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - *Mass Spectrometry
MH  - Molecular Sequence Data
MH  - Parathyroid Hormone/analysis/genetics/metabolism
MH  - Peptides/*analysis
MH  - Protein Structure, Secondary
MH  - Recombinant Proteins/analysis/genetics/metabolism
MH  - Spectrum Analysis, Raman
MH  - Sucrose/chemistry
EDAT- 2012/04/14 06:00
MHDA- 2012/09/20 06:00
CRDT- 2012/04/14 06:00
PHST- 2012/04/14 06:00 [entrez]
PHST- 2012/04/14 06:00 [pubmed]
PHST- 2012/09/20 06:00 [medline]
AID - 10.1021/ac203478r [doi]
PST - ppublish
SO  - Anal Chem. 2012 May 15;84(10):4357-72. doi: 10.1021/ac203478r. Epub 2012 Apr 27.