Determination of Trans-loxoprofen-alcohol Tromethamine in Pregnant SD Rats by a Validated LC-MS/MS Methodï¼Application to a Toxicokinetics and Tissue Distribution Study / Lingling Xu, Wenjun Zhou, Yanjuan Yuan, Qing Shao, Hongqun Qiao
Background: As an anti-inflammatory prodrug, loxoprofen is metabolized into transloprofenol to treat diseases related to pain and inflammation. Although loxoprofen has fewer adverse effects than other NSAIDs, the safety of its usage during pregnancy remains unclear and needs to be considered. Fortunately, the toxicokinetics and tissue distribution study of transloxoprofen- alcohol in pregnant rats can resolve the problem. Objective: The purpose of this study is to establish a simple, sensitive, and effective LC-MS/MS analysis method for determining the concentration of trans-loxoprofen alcohol in plasma and tissues. Methods: The analytic samples were precipitated by methanol in one step and separated using a reverse-phase Poroshell 120 EC-C18 column (4.6 mm×50 mm; 2.7 μm). And the mobile gradient phase at a flow rate of 0.6 mL/min was composed of acetonitrile and 0.1% formic acid in water. The quantitative detection was achieved by multiple-reaction monitoring mode with a positive electrospray ionization source, transitional ion pairs of m/z 265.9>184.8 for trans-loxoprofenalcohol, and 268.8>187.9 for rac-trans-loxoprofen-D3 alcohol (Internal standard). Results: A good linearity of calibration curves for plasma and tissues was observed in the concentration range from 5.0 to 5000 ng/mL, and the lower limit of quantification was detected at 5.0 ng/mL. The intra-day and inter-day precision in plasma and tissues were within 8.94% and 7.26%, respectively. The mean extraction recovery and matrix effects in plasma and tissues were in the range of 89.08~109.27% and 89.00~106.80%, respectively. Precision of stability in plasma and tissues was within 8.91% and 7.08%, respectively. Conclusion: Complying with the requirements of bioanalytical guidelines by validation, this method was successfully adopted to the toxicokinetics and tissue distribution study after intravenously administrated trans-loxoprofen-alcohol into pregnant SD rats.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Current pharmaceutical analysis - 18(2022), 1, Seite 11 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Lingling [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Umfang: |
1 Online-Ressource (11 p) |
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KFL011170034 |
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| 245 | 1 | 0 | |a Determination of Trans-loxoprofen-alcohol Tromethamine in Pregnant SD Rats by a Validated LC-MS/MS Methodï¼Application to a Toxicokinetics and Tissue Distribution Study |c Lingling Xu, Wenjun Zhou, Yanjuan Yuan, Qing Shao, Hongqun Qiao |
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| 520 | |a Background: As an anti-inflammatory prodrug, loxoprofen is metabolized into transloprofenol to treat diseases related to pain and inflammation. Although loxoprofen has fewer adverse effects than other NSAIDs, the safety of its usage during pregnancy remains unclear and needs to be considered. Fortunately, the toxicokinetics and tissue distribution study of transloxoprofen- alcohol in pregnant rats can resolve the problem. Objective: The purpose of this study is to establish a simple, sensitive, and effective LC-MS/MS analysis method for determining the concentration of trans-loxoprofen alcohol in plasma and tissues. Methods: The analytic samples were precipitated by methanol in one step and separated using a reverse-phase Poroshell 120 EC-C18 column (4.6 mm×50 mm; 2.7 μm). And the mobile gradient phase at a flow rate of 0.6 mL/min was composed of acetonitrile and 0.1% formic acid in water. The quantitative detection was achieved by multiple-reaction monitoring mode with a positive electrospray ionization source, transitional ion pairs of m/z 265.9>184.8 for trans-loxoprofenalcohol, and 268.8>187.9 for rac-trans-loxoprofen-D3 alcohol (Internal standard). Results: A good linearity of calibration curves for plasma and tissues was observed in the concentration range from 5.0 to 5000 ng/mL, and the lower limit of quantification was detected at 5.0 ng/mL. The intra-day and inter-day precision in plasma and tissues were within 8.94% and 7.26%, respectively. The mean extraction recovery and matrix effects in plasma and tissues were in the range of 89.08~109.27% and 89.00~106.80%, respectively. Precision of stability in plasma and tissues was within 8.91% and 7.08%, respectively. Conclusion: Complying with the requirements of bioanalytical guidelines by validation, this method was successfully adopted to the toxicokinetics and tissue distribution study after intravenously administrated trans-loxoprofen-alcohol into pregnant SD rats | ||
| 700 | 1 | |a Zhou, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Yanjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Hongqun |e verfasserin |4 aut | |
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