| HIRANUMA APPLICATION DATA | Karl Fischer Titrator | Data No. | KF10 | Apr. 19, 2018 |
| Water contents | Drugs and Medicines – KF Volumetry Direct-Injection Propylene glycol and Glycerin |
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 liquid, generally 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.
Examples for water contents measurements of propylene glycol and glycerin 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 | |
| (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) | Wash the syringe with sample. |
| (4) | Draw the sample into syringe and then weigh the syringe. |
| (5) | Inject sample from rubber septum of titration cell as shown in Fig.3.2. |
| (6) | Start titration. Measurement parameter is shown in Table 4.1. |
| (7) | Weigh the syringe again and then set the difference of weight to sample size. |
Fig.3.1 Preparation of the reagents
Fig.3.2 Injection of sample
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 | 0 | min |
| KF Factor | 5.7614 | 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 | |
| Solvent | S,O,CE | |
| 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(ppm) |
Statistics result | Remark | |
| Propylene glycol | 2.0482 | 0.30 | 1.728 | 843.7 | Avg. | 860.9 ppm | KF Factor |
| 2.0517 | 0.31 | 1.786 | 870.5 | SD | 14.9 ppm | 5.7614 mg/mL | |
| 1.9240 | 0.29 | 1.671 | 868.5 | RSD | 1.73 % | ||
| Glycerin | 6.9553 | 1.27 | 7.259 | 1043.7 | Avg. | 1047.6 ppm | KF Factor |
| 7.0613 | 1.29 | 7.374 | 1044.3 | SD | 6.3 ppm | 5.7160 mg/mL | |
| 7.1525 | 1.32 | 7.545 | 1054.9 | RSD | 0.60 % | ||
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 |
