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Optimization of analytical methods for analysis of the antimalarial drug piperaquine
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. University of California San Francisco.
2013 (English)Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Introduction:  Piperaquine (PQ) is an antimalarial drug used in preventive treatment and combination therapy as a partner drug in dihydroartemisinin-piperaquine (DP). In young children the pharmacokinetics (PK) of PQ seem to differ from adults resulting in a lower efficacy of the drug than expected. Finger prick capillary dried blood spots (DBS) are being used more and more in PK analysis. They are simpler to collect, store and transport than plasma samples and require less blood taken from the patient. Concentrations of PQ are higher in capillary blood than in plasma. A correlation between DBS and venous plasma measurements must be defined before DBS can be used as a field-study tool. Aim: To compare PQ concentrations generated from DBS and simultaneously collected venous plasma samples and determine if DBS give reliable results and can be used in PK-PD investigations in large cohort-studies. Materials and Methods:  LC-MS/MS methods for quantifying PQ in plasma and DBS were developed. Samples collected from young children receiving monthly DP treatment, in a cohort study in Uganda, were analyzed. Correlation analysis was performed with Stata® including plasma samples analyzed with the plasma method developed in 2013 and DBS samples analyzed previously with a semi-quantitative method in the pilot work in 2012. Results:  82 paired samples were used in the correlation analysis. Preliminary results from the linear regression analysis show a mean ratio of 4.08, STD of 3.37 and a R2-value of 0.37. Conclusions:  The DBS method must be fully validated and used for analyzing the remaining DBS samples (~80) as well as reanalyzing the DBS samples analyzed in the pilot work (~350). A new regression analysis using all data must be done in order to assess the correlation between PQ concentrations in plasma and DBS samples.

Place, publisher, year, edition, pages
2013. , 32 p.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-221872OAI: oai:DiVA.org:uu-221872DiVA: diva2:710250
Subject / course
Pharmacokinetics
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2014-04-07 Created: 2014-04-05 Last updated: 2014-04-07Bibliographically approved

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