Simultaneous Determination of Nirmatrelvir and Ritonavir in Human Plasma by HPLC-MS/MS
Bibliographic record
Abstract
Introduction. SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) is expected to remain a persistent global threat. Therefore, development of coronavirus disease 2019 (COVID-19) drugs is the most urgent global issue. Nirmatrelvir and ritonavir combination is an oral antiviral drug combination with activity against SARS-CoV-2. Nirmatrelvir and ritonavir combination is highly efficacious in reducing the risk of COVID-19. The study describes development and validation of high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of nirmatrelvir and ritonavir in human blood plasma. The method could be applied in pharmacokinetic study of nirmatrelvir and ritonavir. Aim. The aim of this study is to develop and validate a HPLC-MS/MS bioanalytical method for the determination of nirmatrelvir and ritonavir in human plasma. Materials and methods. The determination of nirmatrelvir and ritonavir in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: promethazine. Mobile phase: 0.1% formic acid solution in water (Eluent A), 0.1% formic acid in acetonitrile (Eluent B). Column: Phenomenex Luna C18 50 × 2.0 mm, 5 μm. Analytical range: 50.00–10000.00 ng/mL for nirmatrelvir, 5.00–1000.00 ng/mL for ritonavir in human plasma. Ionization source and ionization: electrospray ionization, positive. Detection conditions: 499.90 → 110.10 m/z, 499.90 → 319.20 m/z (nirmatrelvir), 720.90 → 426.00 m/z, 720.90 → 296.20 m/z, 720.90 → 268.10 m/z, 720.90 → 197.10 m/z, 720.90 → 139.90 m/z (ritonavir), 285.15 → 198.05 m/z (promethazine). Results and discussion. This method was validated for selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. Conclusion. The HPLC-MS/MS method for quantitative determination of nirmatrelvir and ritonavir in human plasma was developed and validated. The analytical range was 50.00–10000.00 ng/mL for nirmatrelvir, 5.00–1000.00 ng/mL for ritonavir in human plasma. This method was applied to investigate the pharmacokinetics of nirmatrelvir and ritonavir.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".