The Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry Method for Detection and Quantification of C4NP in Rat Plasma and Its Application to Pharmacokinetic Studies
Bibliographic record
Abstract
INTRODUCTION: Combretastatins, which are excellent anticancer agents, are isolated from Combretum. A sensitive ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for the pharmacokinetic study of a combretastatin analog (C4NP) in rats. METHODS: Sample pretreatment was finished by simple protein precipitation in which methanol was added to plasma containing an internal standard (buspirone hydrochloride). Liquid chromatograph separation was accomplished on a reverse-phase Kinetex XB-C18 column [50×4.6 mm; internal diameter: 2.6 μm (Phenomenex, Torrance, CA, U.S.A.)] with a gradient mobile phase of acetonitrile (0.05% formic acid, volume for volume) and water (0.05% formic acid) at a flow rate of 0.3 mL/min. The analytes were analyzed in the positive ion by electrospray ionization and quantified in the selective reaction monitoring mode. The entire procedure was validated following the U.S. Food and Drug Administration guidelines for bioanalytical methods validation. RESULTS: Our study investigated, for the first time, the detection and pharmacokinetic characteristics of C4NP in Sprague-Dawley rat plasma. The pharmacokinetic results suggest that C4NP is predominantly restricted to blood or extracellular fluid and is not extensively distributed to most organ tissues. In addition, C4NP can be cleared by renal filtration and active tubular secretion in Sprague-Dawley rats. Toxicokinetics of C4NP in these rats indicate that no saturation of the metabolic or excretion process occurs for C4NP, and metabolic induction and accumulation of toxic injury from multiple dosing are both absent. CONCLUSIONS: For 100 μL of analyte, recovery plus high accuracy and reproducibility indicate that our new ultra-performance liquid chromatography tandem mass spectrometry method is a reliable and high-throughput analytical tool for the pharmacokinetic study of C4NP in rats. Those results should be useful for risk assessment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".