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Chromatography of Therapeutic Peptides - Contrasting SFC and HPLC
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
2019 (Engelska)Självständigt arbete på avancerad nivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
Abstract [en]

This work is a comparison of a well-established and a novel, "green" and efficient technique to separate peptides of pharmaceutical interest. An attempt is made to derive the chromatographic retention behaviour from these techniques to a number of property descriptors derived from the linear sequence of amino acids. A set of therapeutic peptides were carefully chosen to be experimentally evaluated using in silico-based descriptor calculations. A principle component analysis was performed to assess the distribution of calculated descriptors for including peptides with variable properties. A diluent optimization study was also included to find the optimal diluent for peptides with minimal diluent effects and peak splitting phenomena. The results showed that the solvents tert-butanol and methanol performed best between 20-30 and 50 volumetric percent water as additive in SFC and HPLC, respectively. These diluents were then used for the peptides within the set to evaluate the retention and selectivity in HPLC and SFC. SFC performed well in terms of resolving power. Inparticular, SFC was able to separate Leuprolide and Triptorelin while HPLC was not. A comparison was also made in between the two stationary phases CN and XT, where a global selectivity was shown to be higher for CN.

This work does also assess a novel method for determining solubility of analytes in supercritical fluid. The method was evaluated using the pharmaceutical compounds caffeine and aspirin and then used to determine solubility of Leu-Enkephalin in 20% (v/v%) methanol. The solubility of caffeine was determined to be 0.45 mg ml-1 in pure SF-CO2 under 140 bar pressure and 3.9 mg ml-1 for aspirin in 2.4% methanol. Both values correlated well with measurements from four acknowledged papers within this field. Leu-Enkephalin was found to have a solubility of 1.90 mg ml-1 using a solvent corresponding to the initial phase condition of the gradient used for peptide analysis in SFC. Further experimental work is required before the method can be implemented as a useful tool in preparative chromatography, however the results presented here show the compatibility of assessing biomolecules in both pure SF-CO2 and mixed with modifier. The possibility to determine solubility with additional modifier infers an important step of including and evaluating these compounds creating a solid support to subsequent large scale separation.

Ort, förlag, år, upplaga, sidor
2019.
Serie
UPTEC X ; 19036
Nationell ämneskategori
Industriell bioteknik Biokemi och molekylärbiologi Medicinsk laboratorie- och mätteknik
Identifikatorer
URN: urn:nbn:se:uu:diva-390890OAI: oai:DiVA.org:uu-390890DiVA, id: diva2:1343046
Externt samarbete
Early Chemical Development, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca
Utbildningsprogram
Civilingenjörsprogrammet i molekylär bioteknik
Handledare
Examinatorer
Tillgänglig från: 2019-08-16 Skapad: 2019-08-15 Senast uppdaterad: 2019-08-16Bibliografiskt granskad

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Farmakognosi
Industriell bioteknikBiokemi och molekylärbiologiMedicinsk laboratorie- och mätteknik

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