Determination of water content in lyophilized powder drugs using Karl Fischer titration
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Objective: To verify the feasibility, accuracy, and reproducibility of AKF-1 in determining the moisture content in freeze-dried powder drugs through this experiment. http://www.lab-info.com/uploads/200817/1-200QG12452a3.jpg Instrument configuration 1. AKF-1 Karl Fischer moisture analyzer main unit ； 2. Fully enclosed safety titration cell assembly ； 3. Dual-platinum sheet electrode ； 4. Titrating cell stirring platform ； 5. 10μL micro injection needle ； 6. Electronic balance (0.1mg) ； Reagent 1. Titrant: Single-component reagent for volumetric analysis (Concord 1504, equivalent weight 2.5 mg/mL) ； 2. Solvent: Methanol (Shanghai Xingke Chemical, HPLC grade) ； 3. Auxiliary reagents: None ； Measurement method 1. Use the instrument’s “solvent absorption” function to inject approximately 50 ml of anhydrous methanol solution into the titration cell. 2. Use the instrument’s “blank” function to titrate to the endpoint in order to remove moisture from the titration cell; the instrument is then ready and remains at the endpoint status. 3. Use a dried micro-syringe to accurately draw 10 μL of pure water; dry the tip of the syringe and then place it on a balance for weighing. Select the instrument’s calibration function, pour the pure water below the liquid level in the titration cell, dry the syringe tip again and weigh it, and use the difference between the two weights as the weight of the pure water to input into the instrument in order to start the calibration process. 4. Repeat Step 3, taking 3 to 5 measurements in total; the instrument will automatically save the calibration results and calculate the average value as the titrability of the reagent. 5. Take 3 vials of lyophilized powder (30 mg per vial), open them, use a stirring rod to break up any lumps in the lyophilized powder, pour it out, weigh it, and then add it to the titration cell of the moisture meter. Enter the weight of the sample and start the measurement; once the measurement is complete, the moisture content of the sample is obtained. Instrument parameters:1. Volume of the measuring tube: 20 mL
2. Endpoint current value: 60 μA
3. Minimum volume of liquid to be injected: 0.001 mL
4. Titration delay: 300 s
5. Endpoint delay: 10 s
6. Drift correction: On
7. Endpoint holding: On
Record of sample analysis using the Karl Fischer moisture analyzer:
Sample source: Provided by a user in Shanghai
Environmental humidity: 50%
Environmental temperature: 16 ℃
Current drift rate: 22 μL/min
Sample name: Lyophilized powder injection
Titrability: 2.45 mg/mL
Sequence of measurements:
| No. | Amount injected (mg) | Titration volume (mL) | Moisture content (mg) | Measurement time (m:s) | Result (%) |
|-----|----------------------|------------------------|-----------------------|------------------------|------------|
| 1 | 88.1 | 0.417 | 1.018 | 6:46 | 1.156 |
| 2 | 87.7 | 0.397 | 0.972 | 6:45 | 1.108 |
| 3 | 88.6 | 0.429 | 1.053 | 6:40 | 1.188 |
| 4 | 86.9 | 0.426 | 1.044 | 6:37 | 1.201 |
| 5 | 89.0 | 0.427 | 1.045 | 6:40 | 1.176 |
| 6 | 88.9 | 0.404 | 0.990 | 6:44 | 1.114 |
Average value: 1.157%
RSD: 3.349%
Additional notes: Moisture content in lyophilized powders can be determined using either the coulometric or volumetric method. Since the coulometric method can easily contaminate the electrolytic cell, the volumetric method was used in this study; it facilitates solvent replacement. However, to achieve the required precision, a larger amount of sample is needed in the volumetric method compared to the coulometric method, which increases sample consumption. For some expensive lyophilized drugs, users may consider using the coulometric method after weighing the pros and cons. To prevent the lyophilized powder from absorbing moisture, it should be tested as soon as possible after the bottle cap is opened.