24/7 Therapeutic Drug Monitoring of Beta-Lactam Antibiotics with CLAM-2000
Abstract
:1. Introduction
2. Results
2.1. Validation of HPLC Assays (Chromatography)
2.2. Linearity
2.3. Accuracy and Imprecision
2.4. Stability Studies
2.5. Method Correlation
2.6. Selectivity and Specificity Studies
2.7. Robustness
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Matrix Effects
4.3. Analysis of Beta-Lactam Antibiotics in a 24/7 Environment (CLAM-2000)
4.3.1. Sample Preparation
4.3.2. Separation (Chromatographic Conditions)
4.3.3. Mass Spectrometry
4.3.4. Validation Assay
4.3.5. Accuracy and Precision
4.3.6. Linearity
4.3.7. Stability and Robustness
4.4. Comparison with Routine Method
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Analyte | Y | R2 | Range (mg/L) |
---|---|---|---|
Ceftazidime | 1.0086x − 0.7149 | 0.9992 | 0.5–156 |
Cefotaxime | 0.9888x − 0.4574 | 0.9961 | 0.5–156 |
Flucloxacillin | 1.0374x + 0.7133 | 0.9987 | 0.5–156 |
Meropenem | 1.0033x + 0.2383 | 0.9994 | 0.5–62.5 |
Piperacillin | 0.9758x + 2.0205 | 0.9932 | 0.5–156 |
Sample | Concentration (mg/L) | Nominal Value (mg/L) | Concentration Found (mg/L) (Mean ± SD) | Imprecision CV (%) | Bias d (%) |
---|---|---|---|---|---|
Ceftazidime | |||||
LLOQ | 0.35 | 0.35 | 0.3 ± 0.04 | 11.7 | 3.9 |
QC 1 | 10 | 10 | 10.5 ± 1.0 | 9.5 | −4.5 |
QC 2 | 25 | 25 | 25.5 ± 2.1 | 8.03 | −1.9 |
QC 3 | 50 | 51 | 49 ± 4 | 8.2 | 3.9 |
QC 4 | 150 | 191 | 174.6 ± 17.9 | 10.3 | −8.6 |
Cefotaxime | |||||
LLOQ | 0.5 | 0.5 | 0.5 ± 0.03 | 6.1 | 3.5 |
QC 1 | 10 | 8.7 | 9 ± 0.3 | 3.1 | −3.2 |
QC 2 | 25 | 20 | 20.3 ± 0.8 | 3.7 | −1.6 |
QC 3 | 50 | 46 | 47.4 ± 2.2 | 4.6 | −3.1 |
QC 4 | 150 | 163 | 161.4 ± 9.4 | 5.8 | −1 |
Flucloxacillin | |||||
LLOQ | 0.5 | 0.5 | 0.5 ± 0.04 | 7.9 | 5.8 |
QC 1 | 10 | 9 | 8.9 ± 0.5 | 5.2 | 1.7 |
QC 2 | 25 | 25 | 24.3 ± 1.6 | 6.6 | 2.9 |
QC 3 | 50 | 46 | 46.4 ± 2.4 | 5.2 | −0.9 |
QC 4 | 150 | -- | -- | -- | -- |
Meropenem | |||||
LLOQ | 0.5 | 0.5 | 0.5 ± 0.02 | 4.2 | 0.9 |
QC 1 | 10 | 10 | 10.2 ± 0.5 | 4.6 | −2 |
QC 2 | 25 | 25 | 24.1 ± 1.1 | 4.6 | 3.5 |
QC 3 | 50 | 50 | 51.9 ± 2.5 | 4.9 | −3.8 |
QC 4 | 150 | 160 | 162.2 ± 3.9 | 2.4 | 1.4 |
Piperacillin | |||||
LLOQ | 0.5 | 0.5 | 0.5 ± 0.02 | 3.8 | 4.8 |
QC 1 | 10 | 12 | 11.5 ± 0.5 | 4.6 | 4 |
QC 2 | 25 | 28 | 28 ± 0.7 | 2.5 | −0.1 |
QC 3 | 50 | 55 | 56± 1.6 | 2.8 | −1.8 |
QC 4 | 150 | 150 | 142.8 ± 2.3 | 1.6 | −4.8 |
Sample | Concentration (mg/L) | Nominal Value (mg/L) | Concentration Found (mg/L) (Mean ± SD) | Imprecision CV (%) | Bias d (%) |
---|---|---|---|---|---|
Ceftazidime | |||||
QC 1 | 10 | 10 | 10.5 ± 0.8 | 7.2 | 4.6 |
QC 2 | 25 | 25 | 26.7 ± 1.7 | 6.3 | 6.9 |
QC 3 | 50 | 51 | 49.9 ± 4.8 | 9.7 | 2.2 |
QC 4 | 150 | 191 | 179.2 ± 13.1 | 7.3 | 6.2 |
Cefotaxime | |||||
QC 1 | 10 | 8.7 | 8.8 ± 0.1 | 1.6 | 0.6 |
QC 2 | 25 | 20 | 19.7 ± 0.7 | 3.8 | 1.5 |
QC 3 | 50 | 46 | 46.7 ± 0.9 | 2 | 1.4 |
QC 4 | 150 | 163 | 164.8 ± 6.2 | 3.8 | 1.1 |
Flucloxacillin | |||||
QC 1 | 10 | 10 | 9 ± 0.4 | 4.04 | 1 |
QC 2 | 25 | 25 | 24.9 ± 1.5 | 6.03 | 0.5 |
QC 3 | 50 | 46 | 47.2 ± 2.5 | 5.3 | 2.6 |
QC 4 | 150 | -- | -- | -- | -- |
Meropenem | |||||
QC 1 | 10 | 10 | 10.1 ± 0.3 | 2.8 | 0.5 |
QC 2 | 25 | 23 | 22.9 ± 0.6 | 2.5 | 0.3 |
QC 3 | 50 | 50 | 50.6 ± 2 | 3.9 | 1.2 |
QC 4 | 150 | 160 | 169.2 ± 5.1 | 3 | 5.8 |
Piperacillin | |||||
QC 1 | 10 | 10 | 10.5 ± 0.3 | 3.2 | 5.2 |
QC 2 | 25 | 28 | 25.7 ± 1.1 | 4.2 | 8.1 |
QC 3 | 50 | 55 | 51 ± 1.1 | 2.2 | 5 |
QC 4 | 150 | 180 | 179.4 ± 8.8 | 7.3 | 0.4 |
Analyte | c (mg/L) | CV (%) | d (%) |
---|---|---|---|
Ceftazidime | 10 | 9.5 | 4.5 |
25 | 8.0 | 1.9 | |
50 | 8.2 | 3.9 | |
Cefotaxime | 9 | 3.1 | 1.6 |
20 | 3.7 | 1.6 | |
46 | 4.6 | 3.9 | |
Flucloxacillin | 9 | 5.2 | 1.7 |
25 | 6.6 | 2.9 | |
46 | 5.2 | 0.9 | |
Meropenem | 10 | 4.6 | 2.0 |
25 | 4.6 | 3.5 | |
50 | 4.9 | 3.8 | |
Piperacillin | 12 | 4.6 | 4.0 |
28 | 2.5 | 0.1 | |
55 | 2.8 | 1.8 |
Analyte | n | R | Slope (b) | Intercept (a) | Range MSMS | Range CLAM-2000 |
---|---|---|---|---|---|---|
Ceftazidime | 39 | 0.994 | 0.993 | −0.605 | 3.1–187 | 2.9–196 |
Cefotaxime | 19 | 0.994 | 0.959 | 0.956 | 4.6–54 | 4.6–52 |
Flucloxacillin | 20 | 0.981 | 0.924 | −0.269 | 9.8–47.9 | 8.3–49.6 |
Meropenem | 30 | 0.981 | 1.058 | −9.41 | 5.4–155 | 4.8–190 |
Piperacillin | 36 | 0.983 | 1.076 | −5.03 | 29.1–343 | 22–350.9 |
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Khromov, T.; Dihazi, G.H.; Brockmeyer, P.; Fischer, A.; Streit, F. 24/7 Therapeutic Drug Monitoring of Beta-Lactam Antibiotics with CLAM-2000. Antibiotics 2023, 12, 1526. https://doi.org/10.3390/antibiotics12101526
Khromov T, Dihazi GH, Brockmeyer P, Fischer A, Streit F. 24/7 Therapeutic Drug Monitoring of Beta-Lactam Antibiotics with CLAM-2000. Antibiotics. 2023; 12(10):1526. https://doi.org/10.3390/antibiotics12101526
Chicago/Turabian StyleKhromov, Tatjana, Gry Helene Dihazi, Phillipp Brockmeyer, Andreas Fischer, and Frank Streit. 2023. "24/7 Therapeutic Drug Monitoring of Beta-Lactam Antibiotics with CLAM-2000" Antibiotics 12, no. 10: 1526. https://doi.org/10.3390/antibiotics12101526