Qualification and Application of a Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometric Method for the Determination of Adalimumab in Rat Plasma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Stocks, Standard (STD) and Quality Control (QC) Samples
2.3. Preparation of Sample Digests for Quantification
2.4. Liquid Chromatography–Mass Spectrometry
2.5. Method Qualification and Sample Analysis Procedure
2.5.1. Calibration Curve, Accuracy and Precision
2.5.2. Species-Dependent Matrix Effect
2.5.3. Freeze and Thaw Stability
2.6. Software
2.7. Application for a Pharmacokinetic Study in Rat
3. Results
3.1. Method Development
3.1.1. Sample Preparation Method
3.1.2. Selection of Target-Specific Signature Peptide
3.1.3. Liquid Chromatography–Mass Spectrometry Analysis Using Quadrupole Time-of-Flight mass spectrometer
3.2. Method Qualification
3.2.1. Calibration Curve, Linearity and Sensitivity
3.2.2. Accuracy, Precision and Species-Dependent Matrix Effect
3.2.3. Freeze and Thaw Stability
3.2.4. Application to a Pharmacokinetic Study in Rats
4. Discussion
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Run No. | Statistics | QC Low | QC Med | QC High |
---|---|---|---|---|
(2.5 µg/mL) | (25 µg/mL) | (50 µg/mL) | ||
1 | Mean | 2.53 | 25.3 | 52.3 |
Precision (%CV) | 13.1 | 1.76 | 3.54 | |
n | 3 | 3 | 3 | |
Accuracy (%) | 101 | 101 | 105 | |
2 | Mean | 2.73 | 23.9 | 56.3 |
Precision (%CV) | 2.6 | 11.13 | 11.55 | |
n | 3 | 3 | 3 | |
Accuracy (%) | 109 | 95 | 113 | |
3 | Mean | 2.57 | 25.1 | 47.3 |
Precision (%CV) | 17.3 | 10.54 | 4.44 | |
n | 3 | 3 | 3 | |
Accuracy (%) | 103 | 100 | 95 | |
Inter-day | Mean | 2.61 | 24.77 | 51.97 |
Precision (%CV) | 11 | 7.81 | 6.51 | |
n | 9 | 9 | 9 | |
Accuracy (%) | 104 | 99 | 104 |
(a) | |||||
Mouse | Theoretical Concentration (μg/mL) | Mean Concentration (μg/mL) | Precision (%CV) | n | Accuracy (%) |
QC low | 2.5 | 2.85 | 13.2 | 3 | 114 |
QC medium | 25 | 29.4 | 5.74 | 3 | 118 |
QC high | 50 | 57 | 1.43 | 3 | 114 |
(b) | |||||
Monkey | Theoretical Concentration (μg/mL) | Mean Concentration (μg/mL) | Precision (%CV) | n | Accuracy (%) |
QC low | 2.5 | 2.09 | 4.9 | 3 | 84 |
QC medium | 25 | 23.4 | 11.19 | 3 | 94 |
QC high | 50 | 48.1 | 5.12 | 3 | 96 |
(a) | |||||
Rat | Theoretical Concentration (μg/mL) | Mean Concentration (μg/mL) | Precision (%) | n | Accuracy (%) |
QC low | 2.5 | 2.58 | 10.5 | 3 | 103 |
QC medium | 25 | 25.6 | 13.67 | 3 | 102 |
QC high | 50 | 57.3 | 8.73 | 3 | 115 |
(b) | |||||
Mouse | Theoretical Concentration (μg/mL) | Mean Concentration (μg/mL) | Precision (%) | n | Accuracy (%) |
QC low | 2.5 | 2.62 | 16.7 | 3 | 105 |
QC medium | 25 | 28 | 3.26 | 3 | 112 |
QC high | 50 | 60.2 | 0.94 | 3 | 120 |
(c) | |||||
Monkey | Theoretical Concentration (μg/mL) | Mean Concentration (μg/mL) | Precision (%) | n | Accuracy (%) |
QC low | 2.5 | 2.26 | 2.8 | 3 | 91 |
QC medium | 25 | 19.5 | 12.42 | 3 | 78 |
QC high | 50 | 40.3 | 8.52 | 3 | 81 |
PK parameters | ||||||||
---|---|---|---|---|---|---|---|---|
Compound | AUC (μg∙Day/mL) | Cl (mL/Day/kg) | Alpha Half Life (Day) | Beta Half Life (Day) | Cmax (μg/mL) | V1 (mL/kg) | Vss (mL/kg) | Compartment Model |
Adalimumab | 155.29 | 6.68 | 0.2 | 9.82 | 41.64 | 24.1 | 85.83 | 2 |
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Park, Y.; Kim, N.; Choi, J.; Park, M.-H.; Lee, B.I.; Shin, S.-H.; Byeon, J.-J.; Shin, Y.G. Qualification and Application of a Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometric Method for the Determination of Adalimumab in Rat Plasma. Pharmaceutics 2018, 10, 61. https://doi.org/10.3390/pharmaceutics10020061
Park Y, Kim N, Choi J, Park M-H, Lee BI, Shin S-H, Byeon J-J, Shin YG. Qualification and Application of a Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometric Method for the Determination of Adalimumab in Rat Plasma. Pharmaceutics. 2018; 10(2):61. https://doi.org/10.3390/pharmaceutics10020061
Chicago/Turabian StylePark, Yuri, Nahye Kim, Jangmi Choi, Min-Ho Park, Byeong Ill Lee, Seok-Ho Shin, Jin-Ju Byeon, and Young G. Shin. 2018. "Qualification and Application of a Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometric Method for the Determination of Adalimumab in Rat Plasma" Pharmaceutics 10, no. 2: 61. https://doi.org/10.3390/pharmaceutics10020061
APA StylePark, Y., Kim, N., Choi, J., Park, M.-H., Lee, B. I., Shin, S.-H., Byeon, J.-J., & Shin, Y. G. (2018). Qualification and Application of a Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometric Method for the Determination of Adalimumab in Rat Plasma. Pharmaceutics, 10(2), 61. https://doi.org/10.3390/pharmaceutics10020061