Automated Stopped-Flow Fluorimetric Sensor for Biologically Active Adamantane Derivatives Based on Zone Fluidics
Abstract
:1. Introduction
2. Results and Discussion
2.1. Reactivity of MEM, AMA, RIM with o-Phthalaldehyde
2.2. Development of the ZF Sensor
2.3. Validation of the ZF Sensor
2.4. Applications of the ZF Sensor
3. Materials and Methods
3.1. Instrumentation
3.2. Reagents and Solutions
3.3. ZF Procedure
3.4. Preparation of Samples
3.5. HPLC-PCD Corroborative Method
4. Conclusions
- This is the first flow-based method for this class of active pharmaceutical ingredients;
- The sensor utilizes commercially available reagents, is simple and straightforward;
- The concept of zone fluidics minimizes the consumption of the samples and reagents compared to continuous flow methods, at a sampling rate of 16 h−1;
- Validation experiments confirmed the suitability of the method for the QC of commercially available formulations;
- A non-EU licensed formulation was found to be out of the specifications set by international pharmacopoeias;
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds mentioned in the text are not available from the authors but they can be purchased from the manufacturers mentioned in the “reagents and solutions” section. |
Variable | Studied Range | Selected Value |
---|---|---|
Instrumental | ||
t (SF)/s | 0–180 | 60 |
V(S)/μL | 50–100 | 100 |
V(R)/μL | 25–100 | 75 |
V(OPA)/μL | 25–100 | 50 |
Chemical | ||
pH | 9.0–12.0 | 10.0 |
c(NAC)/mmol L−1 | 0.5–5.0 | 2.5 |
c(ΟΡΑ)/mmol L−1 | 0.5–10.0 | 5.0 |
Sample | Analyte Concentration (mg L−1) | Placebo Concentration (mg L−1) | Recovery (%) | |
---|---|---|---|---|
AMA | MEM | |||
S1 | 50 | 1000 | 103.6 | 97.2 |
S2 | 100 | 1000 | 101.0 | 99.7 |
S3 | 150 | 1000 | 102.9 | 101.7 |
RIM | ||||
S1 | 5 | 100 | 103.6 | |
S2 | 10 | 100 | 97.1 | |
S3 | 15 | 100 | 101.5 |
Formulation/Sample | Label Content | Specifications | Assay (%) | HPLC (%) |
---|---|---|---|---|
AMA caps (EU) | 100 mg/cap | 95% to 105% | 97.4 (±1.5 a) | 96.1 (±2.2) |
AMA caps (non-EU) | 100 mg/cap | 95% to 105% | 85.3 (±1.2) | 86.9 (±1.8) |
MEM tabs (non-EU) | 5 mg/tab | 95% to 105% | 92.4 (±1.7) | 92.2 (±1.9) |
MEM oral drops (EU) | ||||
Lot1 | 10 mg mL−1 | 95% to 105% | 99.3 (±0.8) | 100.5 (±1.7) |
Lot2 | 10 mg mL−1 | 95% to 105% | 99.5 (±1.2) | 101.2 (±2.6) |
Lot3 | 10 mg mL−1 | 95% to 105% | 98.5 (±1.1) | 99.8 (±2.3) |
Sample | Content Uniformity (%) | ||
---|---|---|---|
AMA Caps (EU) 100 mg/Cap | AMA Caps (Non-EU) 100 mg/Cap | MEM Tabs (Non-EU) 5 mg/Tab | |
S1 | 92.1 (±1.3 a) | 85.4 (±0.6) | 79.8 (±1.5) |
S2 | 98.9 (±0.5) | 84.4 (±0.8) | 85.5 (±1.7) |
S3 | 95.7 (±0.9) | 88.2 (±1.5) | 100.8 (±2.1) |
S4 | 103.3 (±1.8) | 86.7 (±1.0) | 93.5 (±2.2) |
S5 | 96.0 (±1.1) | 85.7 (±1.2) | 82.5 (±1.7) |
S6 | 98.5 (±1.1) | 86.0 (±1.2) | 100.8 (±1.4) |
S7 | 96.4 (±0.9) | 84.5 (±0.6) | 96.2 (±0.9) |
S8 | 94.9 (±1.3) | 84.5 (±0.9) | 86.6 (±2.5) |
S9 | 94.2 (±1.4) | 83.7 (±1.5) | 109.7 (±1.2) |
S10 | 104.2 (±0.8) | 83.9 (±1.7) | 88.6 (±2.1) |
S11 | 85.0 (±1.1) | 92.5 (±1.1) | |
S12 | 84.1 (±1.2) | 96.7 (±1.3) | |
S13 | 85.6 (±0.3) | 89.9 (±0.6) | |
S14 | 83.9 (±0.5) | 87.6 (±0.8) | |
S15 | 83.6 (±0.9) | 96.2 (±1.3) | |
S16 | 85.9 (±0.5) | 88.4 (±0.2) | |
S17 | 86.2 (±1.2) | 100.1 (±0.9) | |
S18 | 84.9 (±1.3) | 87.5 (±1.6) | |
S19 | 84.8 (±0.8) | 90.9 (±1.5) | |
S20 | 86.7 (±1.2) | 106.1 (±1.6) | |
S21 | 82.9 (±1.6) | 88.2 (±0.9) | |
S22 | 85.3 (±0.6) | 88.9 (±0.8) | |
S23 | 85.6 (±0.8) | 90.4 (±1.0) | |
S24 | 85.1 (±0.5) | 105.8 (±1.3) | |
S25 | 84.7 (±1.0) | 89.5 (±1.9) | |
S26 | 85.6 (±1.2) | 91.8 (±1.8) | |
S27 | 86.0 (±0.9) | 91.9 (±2.2) | |
S28 | 84.8 (±1.7) | 105.7 (±2.4) | |
S29 | 83.9 (±1.1) | 90.5 (±1.8) | |
S30 | 85.4 (±1.0) | 85.4 (±0.7) | |
X | 97.4 | 85.1 | 92.9 |
M | 98.5 | 98.5 | 98.5 |
s | 3.9 | 1.1 | 7.4 |
AV | 10.5 | 15.6 | 20.5 |
L1 | 15 | 15 | 15 |
Result | Pass (AV<L1) | Fail (AV>L1) | Fail (AV>L1) |
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Tzanavaras, P.D.; Papadimitriou, S.; Zacharis, C.K. Automated Stopped-Flow Fluorimetric Sensor for Biologically Active Adamantane Derivatives Based on Zone Fluidics. Molecules 2019, 24, 3975. https://doi.org/10.3390/molecules24213975
Tzanavaras PD, Papadimitriou S, Zacharis CK. Automated Stopped-Flow Fluorimetric Sensor for Biologically Active Adamantane Derivatives Based on Zone Fluidics. Molecules. 2019; 24(21):3975. https://doi.org/10.3390/molecules24213975
Chicago/Turabian StyleTzanavaras, Paraskevas D., Sofia Papadimitriou, and Constantinos K. Zacharis. 2019. "Automated Stopped-Flow Fluorimetric Sensor for Biologically Active Adamantane Derivatives Based on Zone Fluidics" Molecules 24, no. 21: 3975. https://doi.org/10.3390/molecules24213975