Quantitation of Free and Total Amphotericin B in Human Biologic Matrices by a Liquid Chromatography Tandem Mass Spectrometric Method
Bibliographic record
Abstract
Amphotericin B remains the standard of care for the treatment of invasive and disseminated fungal infections. Various lipid-based formulations of amphotericin B have been developed to improve its therapeutic index by decreasing toxicity. Previous bioanalytic methods using microbial inhibition or high-pressure liquid chromatography quantified total amphotericin B (free, plasma protein-bound, and lipid-complexed). Sensitivity of this method with a low limit of quantitation of 0.05 microg/mL was inadequate to determine free (unbound) amphotericin B. A sensitive LC/MS/MS method was developed to determine the total amphotericin B value in human plasma and other biologic matrices and the free amphotericin B concentration in plasma. For determination of total plasma amphotericin B concentrations, the sample was diluted and injected onto the LC/MS/MS. For total amphotericin B in other matrices and free amphotericin B in plasma, solid-phase extraction was used. Natamycin served as an internal standard. A PE Sciex API 3000 (Sciex; Concord, Ontario, Canada) was used to assess free amphotericin B in plasma ultrafiltrate determination and an API 3+ for the other matrices, with electrospray interfaced to a C18 analytic column. The low limit of quantitation was 1 ng/mL for ultrafiltrate. For total amphotericin B, the low limits were 2 microg/mL for plasma, 0.05 microg/mL for urine, and 0.4 microg/mL for fecal homogenate. The methods were validated to show the standard range linearity, sensitivity, selectivity, accuracy, precision, and stability of amphotericin B in the matrices tested.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".