A high-throughput LC-MS/MS assay for piperaquine from dried blood spots: Improving malaria treatment in resource-limited settings
Issued Date
2024-01-01
Resource Type
ISSN
2667145X
Scopus ID
2-s2.0-85181884921
Journal Title
Journal of Mass Spectrometry and Advances in the Clinical Lab
Volume
31
Start Page
19
End Page
26
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Mass Spectrometry and Advances in the Clinical Lab Vol.31 (2024) , 19-26
Suggested Citation
Blessborn D., Kaewkhao N., Tarning J. A high-throughput LC-MS/MS assay for piperaquine from dried blood spots: Improving malaria treatment in resource-limited settings. Journal of Mass Spectrometry and Advances in the Clinical Lab Vol.31 (2024) , 19-26. 26. doi:10.1016/j.jmsacl.2023.12.004 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95730
Title
A high-throughput LC-MS/MS assay for piperaquine from dried blood spots: Improving malaria treatment in resource-limited settings
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Abstract
Background: Malaria is a parasitic disease that affects many of the poorest economies, resulting in approximately 241 million clinical episodes and 627,000 deaths annually. Piperaquine, when administered with dihydroartemisinin, is an effective drug against the disease. Drug concentration measurements taken on day 7 after treatment initiation have been shown to be a good predictor of therapeutic success with piperaquine. A simple capillary blood collection technique, where blood is dried onto filter paper, is especially suitable for drug studies in remote areas or resource-limited settings or when taking samples from children, toddlers, and infants. Methods: Three 3.2 mm discs were punched out from a dried blood spot (DBS) and then extracted in a 96-well plate using solid phase extraction on a fully automated liquid handling system. The analysis was performed using LC-MS/MS with a calibration range of 3 – 1000 ng/mL. Results: The recovery rate was approximately 54–72 %, and the relative standard deviation was below 9 % for low, middle and high quality control levels. The LC-MS/MS quantification limit of 3 ng/mL is sensitive enough to detect piperaquine for up to 4–8 weeks after drug administration, which is crucial when evaluating recrudescence and drug resistance development. While different hematocrit levels can affect DBS drug measurements, the effect was minimal for piperaquine. Conclusion: A sensitive LC-MS/MS method, in combination with fully automated extraction in a 96-well plate format, was developed and validated for the quantification of piperaquine in DBS. The assay was implemented in a bioanalytical laboratory for processing large-scale clinical trial samples.