| HIRANUMA APPLICATION DATA | Karl Fischer Titrator | Data No. | KF12 | Apr. 19, 2018 |
| Water contents | Drugs and Medicines – KF Volumetry Powder Sample Sodium Lauryl Sulfate and Benzalkonium Chloride |
1. Abstract
Water contents of drugs and medicines could be determined by Karl Fischer volumetric titrator. In volumetric titration, titrant have a titer which means the capacity to react with water per 1 mL of titrant. Factor is pre-determined before sample measurement and water content of sample is calculated from consumed titrant volume within sample measurement.
When the sample is solid, firstly sample is measured by direct injection into the cell. Dehydrated methanol is used for titration solvent. The titration solvent may change to a composition suitable for dissolving the sample. If the sample is insoluble to titration solvent, heat-evaporation method is appropriate to these samples. An example for water contents measurements of sodium lauryl sulfate and benzalkonium chloride performed by direct injection method are introduced here. The measurement method was determined with reference to Japanese Pharmacopeia.
Reference
1) Japanese Pharmacopoeia Seventeenth Edition
2. Apparatus and Reagents
| (1) | Apparatus | ||
| Titrator | : | HIRANUMA Karl Fischer Volumetric titrator AQV-series or MOIVO-A19 | |
| Electrolytic cell | : | Standard Cell, without drain valne P/N D327511-1 | |
| Powder funnel | : | Outer diameter of leg less than 13 mm | |
| (2) | Reagents | ||
| Titrant | : | HYDRANAL Composite 5 (Honeywell) | |
| Titration solvent | : | HYDRANAL Methanol (Honeywell) |
3. Procedure
| (1) | Fill 50 mL of titration solvent into the titration cell as shown in Fig.3.1. |
| (2) | Start blanking to attain stable background. |
| (3) | Put a sample container, powder funnel and spoon on the balance. Record its read (S₁ [g]). |
| (4) | Open the glass stopper of titration cell lid to introduce the sample with powder funnel as shown in Fig.3.2. |
| (5) | Start titration. Measurement parameter is shown in Table 4.1. |
| (6) | Weigh the sample container, powder funnel and spoon again and record its read (S₂ [g]). The difference of (S₁-S₂ [g]) is set as sample size. |
Fig.3.1 Preparation of the reagents
Fig.3.2 Introduction of sample with powder funnel
4. Parameters and results
Table 4.1 Parameters
| Condition File | ||
| Cal Mode | 0:Sample weight(net) | |
| X=(H-b)xFx1000/SIZE | ||
| Interval Time | 30 | sec |
| Max Volume | 20 | mL |
| Min Feed Vol. | 0.01 | mL |
| S.Timer | 5 | min |
| KF Factor | 5.6884 | mg/mL |
| KF Buret No. | 1 | |
| KF Speed(OUT) | 12 | mL/min |
| KF Speed(IN) | 24 | mL/min |
| Blank Ground | OFF | |
| Sample Size Input | Every Time | |
| Blank Value | 0 | mL |
| Unit Mode | AUTO | |
| E.P Detection | mV | |
| C.P Level | 150 | mV |
| E.P Level | 1 | |
| Auto Interval | 0 | g |
Table 4.2 Results of water content measurement in drugs and medicines
| Sample | Sample size (g) |
Titrant volume(mL) |
Water (mg) |
Water content (%) |
Statistics result | |
| Sodium lauryl sulfate | 0.5162 | 0.75 | 4.266 | 0.8264 | Avg. | 0.8271 % |
| 0.5156 | 0.75 | 4.266 | 0.8274 | SD | 0.0006 % | |
| 0.5156 | 0.75 | 4.266 | 0.8274 | RSD | 0.07 % | |
| Benzalkonium chloride | 0.1005 | 1.38 | 7.850 | 7.8109 | Avg. | 7.8673 % |
| 0.1088 | 1.50 | 8.533 | 7.8428 | SD | 0.0718 % | |
| 0.1002 | 1.40 | 7.964 | 7.9481 | RSD | 0.91 % | |
5. Note
| (1) | Sampling tools should be dried up well before use. |
| (2) | Purge and fill the titrant homogeneously into the buret. |
| (3) | Organic solvents which have relatively high volume expansion coefficient are used as a constituent of titrant. For accurate measurement, factor titration and sample measurement should be performed at the same room temperature as much as possible. |
| Keywords： | Karl Fischer, Volumetric titration, Pharmacopeia |
