Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study
Analytical methods for the quantification of the new 8-aminoquinoline antimalarial tafenoquine (TQ) in human blood, plasma and urine, and the 5,6-orthoquinone tafenoquine metabolite (5,6-OQTQ) in human plasma and urine have been validated. The procedure involved acetonitrile extraction of samples fo...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/23/8186 |
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| author | Geoffrey W. Birrell Karin Van Breda Bridget Barber Rebecca Webster James S. McCarthy G. Dennis Shanks Michael D. Edstein |
| author_facet | Geoffrey W. Birrell Karin Van Breda Bridget Barber Rebecca Webster James S. McCarthy G. Dennis Shanks Michael D. Edstein |
| author_sort | Geoffrey W. Birrell |
| collection | DOAJ |
| description | Analytical methods for the quantification of the new 8-aminoquinoline antimalarial tafenoquine (TQ) in human blood, plasma and urine, and the 5,6-orthoquinone tafenoquine metabolite (5,6-OQTQ) in human plasma and urine have been validated. The procedure involved acetonitrile extraction of samples followed by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Chromatography was performed using a Waters Atlantis T3 column with a gradient of 0.1% formic acid and acetonitrile at a flow rate of 0.5 mL per minute for blood and plasma. Urine analysis was the same but with methanol containing 0.1% formic acid replacing acetonitrile mobile phase. The calibration range for TQ and 5,6-OQTQ in plasma was 1 to 1200 ng/mL, and in urine was 10 to 1000 ng/mL. Blood calibration range for TQ was 1 to 1200 ng/mL. Blood could not be validated for 5,6-OQTQ due to significant signal suppression. The inter-assay precision (coefficient of variation %) was 9.9% for TQ at 1 ng/mL in blood (<i>n</i> = 14) and 8.2% for TQ and 7.1% for 5,6-OQTQ at 1 ng/mL in plasma (<i>n</i> = 14). For urine, the inter-assay precision was 8.2% for TQ and 6.4% for 5,6-OQTQ at 10 ng/mL (<i>n</i> = 14). TQ and 5,6-OQTQ are stable in blood, plasma and urine for at least three months at both −80 °C and −20 °C. Once validated, the analytical methods were applied to samples collected from healthy volunteers who were experimentally infected with <i>Plasmodium falciparum</i> to evaluate the blood stage antimalarial activity of TQ and to determine the therapeutic dose estimates for TQ, the full details of which will be published elsewhere. In this study, the measurement of TQ and 5,6-OQTQ concentrations in samples from one of the four cohorts of participants is reported. Interestingly, TQ urine concentrations were proportional to parasite recrudescence times post dosing To our knowledge, this is the first description of a fully validated method for the measurement of TQ and 5,6-OQTQ quantification in urine. |
| first_indexed | 2024-03-09T17:39:18Z |
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| id | doaj.art-07f064c3dee24f319708a67256df9d7a |
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| publishDate | 2022-11-01 |
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| spelling | doaj.art-07f064c3dee24f319708a67256df9d7a2023-11-24T11:38:04ZengMDPI AGMolecules1420-30492022-11-012723818610.3390/molecules27238186Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic StudyGeoffrey W. Birrell0Karin Van Breda1Bridget Barber2Rebecca Webster3James S. McCarthy4G. Dennis Shanks5Michael D. Edstein6Drug Evaluation, Australian Defence Force Malaria and Infectious Disease Institute, Brisbane 4051, AustraliaDrug Evaluation, Australian Defence Force Malaria and Infectious Disease Institute, Brisbane 4051, AustraliaClinical Malaria Group, QIMR Berghofer Medical Research Institute, Brisbane 4006, AustraliaClinical Malaria Group, QIMR Berghofer Medical Research Institute, Brisbane 4006, AustraliaClinical Malaria Group, QIMR Berghofer Medical Research Institute, Brisbane 4006, AustraliaDrug Evaluation, Australian Defence Force Malaria and Infectious Disease Institute, Brisbane 4051, AustraliaDrug Evaluation, Australian Defence Force Malaria and Infectious Disease Institute, Brisbane 4051, AustraliaAnalytical methods for the quantification of the new 8-aminoquinoline antimalarial tafenoquine (TQ) in human blood, plasma and urine, and the 5,6-orthoquinone tafenoquine metabolite (5,6-OQTQ) in human plasma and urine have been validated. The procedure involved acetonitrile extraction of samples followed by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Chromatography was performed using a Waters Atlantis T3 column with a gradient of 0.1% formic acid and acetonitrile at a flow rate of 0.5 mL per minute for blood and plasma. Urine analysis was the same but with methanol containing 0.1% formic acid replacing acetonitrile mobile phase. The calibration range for TQ and 5,6-OQTQ in plasma was 1 to 1200 ng/mL, and in urine was 10 to 1000 ng/mL. Blood calibration range for TQ was 1 to 1200 ng/mL. Blood could not be validated for 5,6-OQTQ due to significant signal suppression. The inter-assay precision (coefficient of variation %) was 9.9% for TQ at 1 ng/mL in blood (<i>n</i> = 14) and 8.2% for TQ and 7.1% for 5,6-OQTQ at 1 ng/mL in plasma (<i>n</i> = 14). For urine, the inter-assay precision was 8.2% for TQ and 6.4% for 5,6-OQTQ at 10 ng/mL (<i>n</i> = 14). TQ and 5,6-OQTQ are stable in blood, plasma and urine for at least three months at both −80 °C and −20 °C. Once validated, the analytical methods were applied to samples collected from healthy volunteers who were experimentally infected with <i>Plasmodium falciparum</i> to evaluate the blood stage antimalarial activity of TQ and to determine the therapeutic dose estimates for TQ, the full details of which will be published elsewhere. In this study, the measurement of TQ and 5,6-OQTQ concentrations in samples from one of the four cohorts of participants is reported. Interestingly, TQ urine concentrations were proportional to parasite recrudescence times post dosing To our knowledge, this is the first description of a fully validated method for the measurement of TQ and 5,6-OQTQ quantification in urine.https://www.mdpi.com/1420-3049/27/23/8186tafenoquine5,6-orthoquinone tafenoquineanalytical methodurinebloodplasma |
| spellingShingle | Geoffrey W. Birrell Karin Van Breda Bridget Barber Rebecca Webster James S. McCarthy G. Dennis Shanks Michael D. Edstein Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study Molecules tafenoquine 5,6-orthoquinone tafenoquine analytical method urine blood plasma |
| title | Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study |
| title_full | Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study |
| title_fullStr | Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study |
| title_full_unstemmed | Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study |
| title_short | Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study |
| title_sort | quantification of tafenoquine and 5 6 orthoquinone tafenoquine by uhplc ms ms in blood plasma and urine and application to a pharmacokinetic study |
| topic | tafenoquine 5,6-orthoquinone tafenoquine analytical method urine blood plasma |
| url | https://www.mdpi.com/1420-3049/27/23/8186 |
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