A Sensitive Assay for Unbound Docetaxel Using Ultrafiltration plus HPLC-MS and Its Application to a Clinical Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Equipment
2.3. Sample Preparation and HPLC-MS/MS Analysis
2.3.1. Patient Sample Preparation
2.3.2. Quality Control, Standard Curve, and Test Solution Preparation
2.3.3. High-Performance Liquid Chromatography and Mass Spectrometry
2.4. Method Validation
2.4.1. Quantitative analysis of patient samples
2.4.2. Assay Compliance during Patient Sample Analysis
3. Results
3.1. Long-Term Stability
3.2. Precision and Accuracy
3.3. Recovery
3.4. Assay Compliance during Patient Sample Analysis
3.5. Quantitative Analysis of Patient Samples
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Solution/Solvent | Reagent(s) |
---|---|
Reconstitution solution | Acetonitrile:water (20:80, v/v) with 0.1% v/v formic acid |
Extraction solvent | Tert-butyl methyl ether |
Injection solvent | 2-propanol |
Mobile phase A | Acetonitrile:Water (5:95, v/v) with 0.1% v/v formic acid |
Mobile phase B | Acetonitrile:Water (95:5, v/v) with 0.1% v/v formic acid |
Standard curve | Spiked docetaxel (dissolved in ethanol) in human plasma to 0.084, 0.21, 0.524, 1.311, 3.277, 8.192, 20.48, 51.2, 128, 288, 320 ng/mL |
Internal standard | Paclitaxel dissolved in ethanol–water (50:50, v/v) to 360 ng/mL |
Test solution | Docetaxel at 82 ng/mL and paclitaxel at 96 ng/mL dissolved in ethanol. |
Quality control samples | Docetaxel spiked in human plasma to 0.084 (LLOQ), 0.252 (Low QC), 8 (Med 1 QC), 160 (Med 2 QC) and 256 (High QC) ng/mL. |
(A) | ||
Parameters | ||
Curtain gas (psi) | 30 | |
Collision gas (psi) | 30 | |
Ion spray voltage (volts) | 5500 | |
Temperature (°C) | 300 | |
Ion source gas 1 (psi) | 65 | |
Ion source gas 2 (psi) | 30 | |
(B) | ||
Parameters | Docetaxel | Paclitaxel |
Q1 mass (amu) | 808.4 | 854.5 |
Q3 mass (amu) | 527.2 | 285.0 |
Declustering potential (volts) | 45 | 60 |
Entrance potential (volts) | 4 | 5 |
Collision energy (volts) | 13 | 14 |
Collision cell exit potential (volts) | 14 | 8 |
Nominal Concentration (ng/mL) | ||||
---|---|---|---|---|
7.5 | 32 | 140 | 2000 | |
Actual Concentration Day 131 (ng/mL) | ||||
N = 6 | N = 6 | N = 6 | N = 6 | |
Mean | 8.0 | 32.5 | 144.8 | 1984.1 |
Standard deviation | 0.41 | 2.9 | 9.4 | 100.5 |
Observed change (%) | 6.9% | 1.7% | 3.4% | 0.8% |
Nominal Concentration (ng/mL) | |||||
---|---|---|---|---|---|
LLOQ | Low QC | Med 1 QC | Med 2 QC | High QC | |
QC | 0.084 | 0.252 | 8 | 160 | 256 |
Actual Concentration (ng/mL) | |||||
LLOQ | Low QC | Med 1 QC | Med 2 QC | High QC | |
N | 18 | 18 | 18 | 18 | 18 |
Mean | 0.087 | 0.253 | 8.0 | 158.4 | 254.6 |
SD | 0.011 | 0.024 | 0.64 | 12.1 | 13.8 |
CV | 13.0% | 9.4% | 8.1% | 7.6% | 5.4% |
Accuracy | 10.3% | 7.0% | 6.9% | 6.0% | 4.4% |
Concentration | 82 ng/mL | 82 ng/mL |
Filtration | No | Yes |
N | 3 | 3 |
Mean PAR | 2.9235 | 2.5736 |
SD PAR | 0.1185 | 0.1290 |
Percentage (%) | 88.03 |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Wang, D.; Hughes-Medlicott, N.; Klingler, L.; Wang, Y.; Hung, N.; Duffull, S.; Hung, T.; Glue, P.; Qin, A.; Kwan, R.; et al. A Sensitive Assay for Unbound Docetaxel Using Ultrafiltration plus HPLC-MS and Its Application to a Clinical Study. Pharmaceutics 2024, 16, 602. https://doi.org/10.3390/pharmaceutics16050602
Wang D, Hughes-Medlicott N, Klingler L, Wang Y, Hung N, Duffull S, Hung T, Glue P, Qin A, Kwan R, et al. A Sensitive Assay for Unbound Docetaxel Using Ultrafiltration plus HPLC-MS and Its Application to a Clinical Study. Pharmaceutics. 2024; 16(5):602. https://doi.org/10.3390/pharmaceutics16050602
Chicago/Turabian StyleWang, David, Natalie Hughes-Medlicott, Lilian Klingler, Yi Wang, Noelyn Hung, Stephen Duffull, Tak Hung, Paul Glue, Albert Qin, Rudolf Kwan, and et al. 2024. "A Sensitive Assay for Unbound Docetaxel Using Ultrafiltration plus HPLC-MS and Its Application to a Clinical Study" Pharmaceutics 16, no. 5: 602. https://doi.org/10.3390/pharmaceutics16050602