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Identification and Assessment of Octreotide Acylation in Polyester Microspheres by LC–MS/MS
- Source :
- Pharmaceutical research, 32(9):1685, 3044-3054. Springer New York, Shirangi, M, Hennink, W E, Somsen, G W & Van Nostrum, C F 2015, ' Identification and Assessment of Octreotide Acylation in Polyester Microspheres by LC-MS/MS ', Pharmaceutical research, vol. 32, no. 9, 1685, pp. 3044-3054 . https://doi.org/10.1007/s11095-015-1685-3, Pharmaceutical Research, Pharmaceutical Research, 32(9), 3044. Springer New York LLC
- Publisher :
- Springer Nature
-
Abstract
- Purpose Polyesters with hydrophilic domains, i.e., poly(d,l-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly(l-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic matrices. Our purpose is to assess the extent and sites of acylation of octreotide loaded in microspheres using tandem mass spectrometry analysis. Methods Octreotide loaded microspheres were prepared by a double emulsion solvent evaporation technique. Release profiles of octreotide from hydrophilic microspheres were compared with that of PLGA microspheres. To scrutinize the structural information and localize the actual modification site(s) of octreotide, liquid chromatography ion-trap mass spectrometry (LC-ITMS) was performed on the acylated adducts. Results Hydrophilic microspheres showed less acylated adducts in comparison with PLGA microspheres. LC-MS/MS showed that besides the N-terminus and primary amine of lysine, the primary hydroxyl of the end group of octreotide was also subjected to acylation. Nucleophilic attack of the peptide can also occur to the carbamate bond presented in (PC-PEG-PC)-(PL) since 1,4-butanediisocyanate was used as the chain extender. Conclusions Hydrophilic polyesters are promising systems for controlled release of peptide because substantially less acylation occurs in microspheres based on these polymers. LC-ITMS provided detailed structural information of octreotide modifications via mass analysis of ion fragments. Electronic supplementary material The online version of this article (doi:10.1007/s11095-015-1685-3) contains supplementary material, which is available to authorized users.
- Subjects :
- Polyesters
Octreotide
Pharmaceutical Science
Tandem mass spectrometry
Microsphere
Acylation
chemistry.chemical_compound
Polylactic Acid-Polyglycolic Acid Copolymer
LC–MS/MS
Tandem Mass Spectrometry
Lc ms ms
medicine
acylation
Pharmacology (medical)
Lactic Acid
LC-MS/MS
Glycolic acid
Pharmacology
Chromatography
Organic Chemistry
technology, industry, and agriculture
Microspheres
Lactic acid
Polyester
chemistry
aliphatic polyester
Molecular Medicine
SDG 6 - Clean Water and Sanitation
Polyglycolic Acid
octreotide
Chromatography, Liquid
Research Paper
medicine.drug
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 07248741
- Volume :
- 32
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Research
- Accession number :
- edsair.doi.dedup.....4b0dd0b978e05538099e9ddd48b64e9a
- Full Text :
- https://doi.org/10.1007/s11095-015-1685-3