645 WATER CONDUCTIVITY
Electrical conductivity in water is a measure of the ion-facilitated electron flow through it. Water molecules dissociate into ions as a function of pH and temperature and result in a very predictable conductivity. Some gases, most notably carbon dioxide, readily dissolve in water and interact to form ions, which predictably affect conductivity as well as pH. For the purpose of this discussion, these ions and their resulting conductivity can be considered intrinsic to the water.
Water conductivity is also affected by the presence of extraneous ions. The extraneous ions used in modeling the conductivity specifications described below are the chloride and sodium ions. The conductivity of the ubiquitous chloride ion (at the theoretical endpoint concentration of 0.47 ppm when it was a required attribute test in USP XXII and earlier revisions) and the ammonium ion (at the limit of 0.3 ppm) represent a major portion of the allowed water impurity level. A balancing quantity of cations, such as sodium ions, is included in this allowed impurity level to maintain electroneutrality. Extraneous ions such as these may have significant impact on the water's chemical purity and suitability for use in pharmaceutical applications. The procedure described in the section Bulk Water is designed for measuring the conductivity of waters such as Purified Water, Water for Injection, Water for Hemodialysis, and the condensate of Pure Steam produced in bulk. For water packaged in bulk but manufactured elsewhere or for Sterile Purified Water, Sterile Water for Injection, Sterile Water for Inhalation, and Sterile Water for Irrigation, some additional conductivity tests may be required. Such tests are described in the section Packaged Water.
Online conductivity testing provides real-time measurements and opportunities for real-time process control, decision, and intervention. Precaution should be taken while collecting water samples for off-line conductivity measurements. The sample may be affected by the sampling method, the sampling container, and environmental factors such as ambient carbon dioxide concentration and organic vapors.
INSTRUMENT SPECIFICATIONS AND OPERATING PARAMETERS
Water conductivity must be measured accurately using calibrated instrumentation. The conductivity cell constant, a factor that represents the geometrical properties of the conductivity sensor, must be known within ±2%. The cell constant can be verified directly by using a solution of known or traceable conductivity, or indirectly by comparing the instrument reading taken with the conductivity sensor in question to readings from a conductivity sensor of known or traceable cell constant.
Meter calibration is accomplished by replacing the conductivity sensor with NIST (or equivalent local national authority) -traceable precision resistors (accurate to ±0.1% of the stated value) or an equivalently accurate adjustable resistance device, such as a Wheatstone Bridge, to give a predicted instrument response. Each scale on the meter may require separate calibration prior to use. The frequency of recalibration is a function of instrument design, degree of use, etc. However, because some multiple-scale instruments have a single calibration adjustment, recalibration may be required between each use of a different scale. Excluding the conductivity sensor cell constant accuracy, the instrument accuracy must be ±0.1 µS/cm.
In order to increase the measurement accuracy on the conductivity ranges used, which can be large, and to ensure a complete equipment calibration, it is suggested that periodic verification of the entire equipment be performed. This could be done by comparing the conductivity/resistivity values displayed by the measuring equipment with those of an external calibrated conductivity-measuring device. The two nontemperature-compensated conductivity or resistivity values must be equivalent to within ±20% of each other, or at a difference that is acceptable on the basis of product water criticality and/or the water conductivity ranges in which the measurements are taken. The two conductivity sensors should be positioned close enough together to measure the same water sample in the same environmental conditions.
In addition to the verification method performed in non-temperature-compensated mode, a similar verification performed in temperature-compensated mode could be performed to ensure an appropriate accuracy of the equipment when such a mode is used for trending or other purposes.
Because temperature has a substantial impact on conductivity readings of specimens at high and low temperatures, many instruments automatically correct the actual reading to display the value that theoretically would be observed at the nominal temperature of 25. This is typically done using a temperature sensor embedded in the conductivity sensor and an algorithm in the instrument's circuitry. This temperature compensation algorithm may not be accurate. Conductivity values used in this method are nontemperature-compensated measurements. Temperature measurement is required for the performance of the Stage 1 test. It may be made using the temperature sensor embedded in the conductivity cell sensor. An external temperature sensor positioned near the conductivity sensor is also acceptable. Accuracy of the temperature measurement must be ±2.
The procedure below shall be performed using instrumentation that has been calibrated, has conductivity sensor cell constants that have been accurately determined, and has temperature compensation function that has been disabled. For both online and offline measurements, the suitability of instrumentation for quality control testing is also dependent on the sampling location(s) in the water system. The selected sampling instrument location(s) must reflect the quality of the water used.
The combined conductivities of the intrinsic and extraneous ions vary as a function of pH and are the basis for the conductivity specifications described in the Stage 3pH and Conductivity Requirements table and used when performing Stage 3 of the test method. Two preliminary stages are included in the test method. If the test conditions and conductivity limits are met at either of these preliminary stages, the water meets the requirements of this test. Proceeding to the third stage of the test in these circumstances is unnecessary. Only in the event of failure at the final test stage is the sample judged noncompliant with the requirements of the test.
Stage 1 is intended for online measurement or may be performed offline in a suitable container.
1. Determine the temperature of the water and the conductivity of the water using a nontemperature-compensated conductivity reading.
2. Using the Stage 1Temperature and Conductivity Requirements table, find the temperature value that is not greater than the measured temperature, i.e., the next lower temperature. The corresponding conductivity value on this table is the limit. [noteDo not interpolate.]
3. If the measured conductivity is not greater than the table value, the water meets the requirements of the test for conductivity. If the conductivity is higher than the table value, proceed with Stage 2.
Stage 1Temperature and Conductivity Requirements
(for nontemperature-compensated conductivity measurements only)
4. Transfer a sufficient amount of water (100 mL or more) to a suitable container, and stir the test specimen. Adjust the temperature, if necessary, and, while maintaining it at 25 ± 1, begin vigorously agitating the test specimen while periodically observing the conductivity. When the change in conductivity (due to uptake of atmospheric carbon dioxide) is less than a net of 0.1 µS/cm per 5 minutes, note the conductivity.
5. If the conductivity is not greater than 2.1 µS/cm, the water meets the requirements of the test for conductivity. If the conductivity is greater than 2.1 µS/cm, proceed with Stage 3.
6. Perform this test within approximately 5 minutes of the conductivity determination in Step 5, while maintaining the sample temperature at 25 ± 1. Add a saturated potassium chloride solution to the same water sample (0.3 mL per 100 mL of the test specimen), and determine the pH to the nearest 0.1 pH unit, as directed under pH 791.
7. Referring to the Stage 3pH and Conductivity Requirements table, determine the conductivity limit at the measured pH value. If the measured conductivity in Step 4 is not greater than the conductivity requirements for the pH determined in Step 6, the water meets the requirements of the test for conductivity. If either the measured conductivity is greater than this value or the pH is outside the range of 5.0 to 7.0, the water does not meet the requirements of the test for conductivity.
Stage 3pH and Conductivity Requirements
(for atmosphere- and temperature-equilibrated samples only)
The procedure and test limits are intended for water packaged in bulk but manufactured elsewhere or for Sterile Purified Water, Sterile Water for Injection, Sterile Water for Inhalation, and Sterile Water for Irrigation. All these waters are derived from Purified Water or Water for Injection, and therefore have been determined to be compliant with the Bulk Water requirements before being stored in the container. The specification provided represents the maximum allowable conductivity value, taking into consideration the limitation of the measurement method and reasonable container leaching. Such specification and the sampling volume choices should be defined and validated on the basis of the intended purpose of the water.
Transfer a sufficient amount of water to a suitable container, and stir the test specimen. Adjust the temperature, if necessary, and, while maintaining it at 25 ± 1, begin vigorously agitating the test specimen while periodically observing the conductivity. When the change in conductivity (due to uptake of ambient carbon dioxide) is less than a net of 0.1 µS/cm per 5 minutes, note the conductivity.
For containers with a nominal volume of 10 mL or less, if the conductivity is not greater than 25 µS/cm, the water meets the requirements. For containers with a nominal volume greater than 10 mL, if the conductivity is not greater than 5 µS/cm, the water meets the requirements.