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Development and validation of an enantioselective LC-MS/MS method for the analysis of the anthelmintic drug praziquantel and its main metabolite in human plasma, blood and dried blood spots.
Journal article

Development and validation of an enantioselective LC-MS/MS method for the analysis of the anthelmintic drug praziquantel and its main metabolite in human plasma, blood and dried blood spots.

  • Meister I Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, P.O. Box, CH-4003 Basel, Switzerland.
  • Leonidova A Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, P.O. Box, CH-4003 Basel, Switzerland.
  • Kovač J Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, P.O. Box, CH-4003 Basel, Switzerland.
  • Duthaler U Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, P.O. Box, CH-4003 Basel, Switzerland.
  • Keiser J Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, P.O. Box, CH-4003 Basel, Switzerland. Electronic address: jennifer.keiser@unibas.ch.
  • Huwyler J Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
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  • 2015-10-31
Published in:
  • Journal of pharmaceutical and biomedical analysis. - 2016
Dried blood spot
Enantiomer
LC–MS/MS
Pharmacokinetics
Praziquantel
R-trans-4-OH-PZQ
Anthelmintics
Chromatography, Liquid
Humans
Praziquantel
Reproducibility of Results
Stereoisomerism
Tandem Mass Spectrometry
English Praziquantel (PZQ) is the treatment of choice against various trematode and cestode infections. To study the pharmacokinetics of PZQ in patients infected with the liver fluke Opisthorchis viverrini, we developed and validated an enantioselective liquid chromatography coupled to tandem mass spectrometry method for the analysis of R - and S -PZQ and its R -trans-4-OH-PZQ metabolite in human plasma, blood and dried blood spots (DBS). The analytes were detected in the positive mode using selected reaction monitoring (R- and S-PZQ: m/z 312.2 → 202.2; R-trans -4-OH-PZQ: m/z 328.0 → 202.0). Prior to the chiral separation with a cellulose tris(3-chloro-4-methylphenylcarbamate) column, the analytes were purified from matrix contaminants and concentrated on a C-18 trapping column. The analytical range for each PZQ enantiomer was 0.01-2.5 μg/mL, and 0.1-25 μg/mL for the metabolite. The method met the requirements regarding precision (± 15%, ± 20% at the lower limit of quantification-LLOQ), intra- and inter-assay accuracy (85-115%, 80-120% at LLOQ), and linearity (R(2) ≥ 0.998). The analytes were stable in stock solutions as well as in plasma, blood and DBS. For DBS, the influences of hematocrit and blood spot size were considered as minor. Our validation results show that the method presented here is precise, accurate and selective, and can be used for pharmacokinetic studies. Moreover, the enantioselective separation was achieved with a run time of 11.5 min and a simple sample processing method.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/270205
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