Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) Assay for the Determination of Total and Unbound Ciprofloxacin Concentrations in Human Plasma
Bibliographic record
Abstract
BACKGROUND: Although unbound ciprofloxacin is responsible for antibacterial effects, assays measuring the unbound drug plasma concentrations are scarce. This study aimed to develop and validate a rapid, reproducible, and sensitive liquid chromatography-tandem mass spectrometry assay for the determination of total and unbound ciprofloxacin plasma concentrations. METHODS: The determination of total ciprofloxacin concentrations required a 10 μL sample, while for unbound ciprofloxacin concentrations, it was 100 μL. Unbound ciprofloxacin was separated from protein-bound ciprofloxacin through ultrafiltration. A deuterated internal standard was used, and the sample preparation involved protein precipitation. The method was fully validated over a concentration range of 0.02-5.0 mg/L, according to the US Food and Drug Administration guidelines. In addition, its clinical application was demonstrated. RESULTS: The total run time was 1.5 minutes. For total ciprofloxacin plasma concentrations, the mean accuracy ranged from 94.5% to 105.0% across the validated range, the intraday imprecision was ≤7.6%, and the interday imprecision was ≤9.8%. For unbound ciprofloxacin plasma concentrations, the mean accuracy ranged from 92.8% to 102.1% across the validated range, the intraday imprecision was ≤7.0%, and the interday imprecision was ≤9.6%. Ciprofloxacin in plasma and ultrafiltrate remained stable for at least 96 hours at room temperature, at least 4 years at -80°C, and at least 3 freeze/thaw cycles (-80°C), with a minimum interval of 24 hours. CONCLUSIONS: The presented method is precise and accurate. It has been implemented in clinical care and research projects at a university hospital, permitting rapid determination of total and unbound ciprofloxacin.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".