Application of negative-ion chemical ionization isotope dilution gas chromatography--mass spectrometry to single-dose bioavailability studies of mefloquine
| Autor: | Ross F. Lawrence, William F. Trager, Kent L. Kunze, J.M. Neal, William N. Howald |
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| Rok vydání: | 1994 |
| Předmět: |
Chemical ionization
Chromatography Chemistry Biological Availability Reproducibility of Results General Chemistry Isotope dilution Mass spectrometry Gas Chromatography-Mass Spectrometry Bioavailability Standard curve Mefloquine Isotopes Humans Gas chromatography Gas chromatography–mass spectrometry Quadrupole mass analyzer |
| Zdroj: | Journal of chromatography. B, Biomedical applications. 661(2) |
| ISSN: | 1572-6495 |
| Popis: | An electron-capture negative-ion chemical ionization gas chromatographic—mass spectrometric assay for mefloquine, an antimalarial drug used in the treatment of drug-resistant Plasmodium falciparum malaria, is described. The method, developed in support of bioavailability studies involving the co-administration of different tableted formulations of the drug and an aqueous solution of its 13 C 3 -labeled analog, enables quantification of both dosage forms. Quantitative analysis of extracted plasma samples was performed on the O- tert. -butyldimethylsilyl ( t -BDMS) derivative of the drug by selected-ion monitoring, using a VG Trio 2000 quadrupole mass spectrometer and monitoring the [M — t -BDMSOH] − ions of the analytes. The method, incorporating [ 2 H 6 ]mefloquine as an internal standard, demonstrated good accuracy and precision over the 1–200 ng ml −1 range, with correlation coefficients greater than 0.990 for all standard curves and a detection level of 50 fg on-column. Replicate analysis of plasma samples over a 90-day period exhibited a mean intra-day and inter-day variation of less than 4.5% and 5.5%, respectively. The high stability and sensitivity of the assay, combined with the inherent selectivity of mass spectrometric detection, make the method well-suited for such studies. |
| Databáze: | OpenAIRE |
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