Nonmonographed Analytical Waters
Both General Notices and Requirements and the introductory section to Reagents, Indicators, and Solutions clearly state that where the term water, without qualification or other specification, is indicated for use in analyses, the quality of water shall be Purified Water. However, numerous such qualifications do exist. Some of these qualifications involve methods of preparation, ranging from specifying the primary purification step to specifying additional purification. Other qualifications call for specific attributes to be met that might otherwise interfere with analytical processes. In most of these latter cases, the required attribute is not specifically tested. Rather, a further purification process is specified that ostensibly allows the water to adequately meet this required attribute.
However, preparation instructions for many reagents were carried forward from the innovator's laboratories to the originally introduced monograph for a particular USPNF article or general test chapter. The quality of the reagent water described in these tests may reflect the water quality designation of the innovator's laboratory. These specific water designations may have originated without the innovator's awareness of the requirement for Purified Water in USPNF tests. Regardless of the original reason for the creation of these numerous special analytical waters, it is possible that the attributes of these special waters could now be met by the basic preparation steps and current specifications of Purified Water. In some cases, however, some of the cited post-processing steps are still necessary to reliably achieve the required attributes.
Users are not obligated to employ specific and perhaps archaically generated forms of analytical water where alternatives with equal or better quality, availability, or analytical performance may exist. The consistency and reliability for producing these alternative analytical waters should be verified as producing the desired attributes. In addition, any alternative analytical water must be evaluated on an application-by-application basis by the user to ensure its suitability. Following is a summary of the various types of nonmonographed analytical waters that are cited in the USPNF.
This water is produced by vaporizing liquid water and condensing it in a purer state. It is used primarily as a solvent for reagent preparation, but it is also specified in the execution of other aspects of tests, such as for rinsing an analyte, transferring a test material as a slurry, as a calibration standard or analytical blank, and for test apparatus cleaning. It is also cited as the starting water to be used for making High Purity Water. Because none of the cited uses of this water imply a need for a particular purity attribute that can only be derived by distillation, water meeting the requirements for Purified Water derived by other means of purification could be equally suitable where Distilled Water is specified.
Freshly Distilled Water
Also called recently distilled water, it is produced in a similar fashion to Distilled Water and should be used shortly after its generation. This implies the need to avoid endotoxin contamination as well as any other adventitious forms of contamination from the air or containers that could arise with prolonged storage. It is used for preparing solutions for subcutaneous test animal injections as well as for a reagent solvent in tests for which there appears to be no particularly high water purity needed that could be ascribable to being freshly distilled. In the test-animal use, the term freshly distilled and its testing use imply a chemical, endotoxin, and microbiological purity that could be equally satisfied by Water for Injection (though no reference is made to these chemical, endotoxin, or microbial attributes or specific protection from recontamination). For nonanimal uses, water meeting the requirements for Purified Water derived by other means of purification and/or storage periods could be equally suitable where recently distilled water or Freshly Distilled Water is specified.
This water is produced by an ion-exchange process in which the contaminating ions are replaced with either H+ or OH ions. Similarly to Distilled Water, Deionized Water is used primarily as a solvent for reagent preparation, but it is also specified in the execution of other aspects of tests, such as for transferring an analyte within a test procedure, as a calibration standard or analytical blank, and for test apparatus cleaning. Also, none of the cited uses of this water imply any needed purity attribute that can only be achieved by deionization. Therefore, water meeting the requirements for Purified Water that is derived by other means of purification could be equally suitable where Deionized Water is specified.
Freshly Deionized Water
This water is prepared in a similar fashion to Deionized Water, though as the name suggests, it is to be used shortly after its production. This implies the need to avoid any adventitious contamination that could occur upon storage. This water is indicated for use as a reagent solvent as well as for cleaning. Due to the nature of the testing, Purified Water could be a reasonable alternative for these applications.
Deionized Distilled Water
This water is produced by deionizing (see Deionized Water ) Distilled Water. This water is used as a reagent in a liquid chromatography test that requires a high purity. Because of the importance of this high purity, water that barely meets the requirements for Purified Water may not be acceptable. High Purity Water (see below) could be a reasonable alternative for this water.
Filtered Distilled or Deionized Water
This water is essentially Purified Water
produced by distillation or deionization that has been filtered through a 1.2-µm rated membrane. This water is used in particulate matter testing where the presence of particles in the water could bias the test results (see Particulate Matter in Injections 788
). Because the chemical water purity needed for this test could also be afforded by water purification processes other than distillation or deionization, filtered water meeting the requirements for Purified Water,
but produced by means other than distillation or deionization could be equally suitable.
This water is Purified Water
that has been filtered to remove particles that could interfere with the analysis where the water is used. Where used for preparing samples for particulate matter testing (see Particulate Matter in Injections 788
), though unspecified in monographs, water filtration should be through a 1.2-µm filter to be consistent with the general test chapter. Where used as a chromatography reagent, monograph-specified filter ratings range from 0.5 µm to unspecified.
High Purity Water
The preparation of this water is defined in Containers 661
. It is water that is prepared by deionizing previously distilled water, and then filtering it through a 0.45-µm rated membrane. This water must have an in-line conductivity of not greater than 0.15 µS/cm (6.67 Megohm-cm) at 25
. For the sake of purity comparison, the analogous Stage 1 and 2 conductivity requirements for Purified Water
at the same temperature are 1.3 µS/cm and 2.1 µS/cm, respectively. The preparation specified in Containers 661
uses materials that are highly efficient deionizers and that do not contribute copper ions or organics to the water, assuring a very high quality water. If the water of this purity contacts the atmosphere even briefly as it is being used or drawn from its purification system, its conductivity will immediately degrade, by as much as about 1.0 µS/cm, as atmospheric carbon dioxide dissolves in the water and equilibrates to bicarbonate ions. Therefore, if the analytical use requires that water purity remains as high as possible, its use should be protected from atmospheric exposure. This water is used as a reagent, as a solvent for reagent preparation, and for test apparatus cleaning where less pure waters would not perform acceptably. However, if a user's routinely available purified water is filtered and meets or exceeds the conductivity specifications of High Purity Water,
it could be used in lieu of High Purity Water.
Functionally, this water must have a negligible ammonia concentration to avoid interference in tests sensitive to ammonia. It has been equated with High Purity Water that has a significantly tighter Stage 1 conductivity specification than Purified Water because of the latter's allowance for a minimal level of ammonium among other ions. However, if the user's Purified Water were filtered and met or exceeded the conductivity specifications of High Purity Water, it would contain negligible ammonia or other ions and could be used in lieu of High Purity Water.
Carbon Dioxide-Free Water
The introductory portion of the Reagents, Indicators, and Solutions section defines this water as Purified Water that has been vigorously boiled for at least 5 minutes, then cooled and protected from absorption of atmospheric carbon dioxide. Because the absorption of carbon dioxide tends to drive down the water pH, most of the uses of Carbon Dioxide-Free Water are either associated as a solvent in pH-related or pH- sensitive determinations or as a solvent in carbonate-sensitive reagents or determinations. Another use of this water is for certain optical rotation and color and clarity of solution tests. Though it is possible that this water is indicated for these tests simply because of its purity, it is also possible that the pH effects of carbon dioxide containing water could interfere with the results of these tests. A third plausible reason that this water is indicated is that outgassing air bubbles might interfere with these photometric-type tests. The boiled water preparation approach will also greatly reduced the concentrations of many other dissolved gases along with carbon dioxide. Therefore, in some of the applications for Carbon Dioxide-Free Water, it could be the inadvertent deaeration effect that actually renders this water suitable. In addition to boiling, deionization is perhaps an even more efficient process for removing dissolved carbon dioxide (by drawing the dissolved gas equilibrium toward the ionized state with subsequent removal by the ion-exchange resins). If the starting Purified Water is prepared by an efficient deionization process and protected after deionization from exposure to atmospheric air, water that is carbon dioxide-free can be effectively made without the application of heat. However this deionization process does not deaerate the water, so if Purified Water prepared by deionization is considered as a substitute water in a test requiring Carbon Dioxide-Free Water, the user must verify that it is not actually water akin to Deaerated Water (discussed below) that is needed for the test. As indicated in the High Purity Water, even brief contact with the atmosphere can allow small amounts of carbon dioxide to dissolve, ionize, and significantly degrade the conductivity and lower the pH. If the analytical use requires the water to remain as pH-neutral and as carbon dioxide-free as possible, even the analysis should be protected from atmospheric exposure. However, in most applications, atmospheric exposure during testing does not significantly affect its suitability in the test.
Ammonia- and Carbon Dioxide-Free Water
As implied by the name, this water should be prepared by approaches compatible with those mentioned for both Ammonia-Free Water and Carbon Dioxide-Free Water. Because the carbon dioxide-free attribute requires post-production protection from the atmosphere, it is appropriate to first render the water ammonia-free using the High Purity Water process followed by the boiling and carbon dioxide-protected cooling process. The High Purity Water deionization process for creating Ammonia-Free Water will also remove the ions generated from dissolved carbon dioxide and ultimately, by forced equilibration to the ionized state, all the dissolved carbon dioxide. Therefore, depending on its use, an acceptable procedure for making Ammonia- and Carbon Dioxide-Free Water could be to transfer and collect High Purity Water in a carbon dioxide intrusion-protected container.
This water is Purified Water
that has been treated to reduce the content of dissolved air by suitable means. In the Reagents
section, approaches for boiling, cooling (similar to Carbon Dioxide-Free Water
but without the atmospheric carbon dioxide protection), and sonication are given as applicable for test uses other than dissolution and drug release testing. Though Deaerated Water
is not mentioned by name in Dissolution 711,
suggested methods for deaerating dissolution media (which may be water) include warming to 41
, vacuum filtering through a 0.45-µm rated membrane, and vigorously stirring the filtrate while maintaining the vacuum. This chapter specifically indicates that other validated approaches may be used. In other monographs that also do not mention Deaerated Water
by name, degassing of water and other reagents is accomplished by sparging with helium. Deaerated Water
is used in both dissolution testing as well as liquid chromatography applications where outgassing could either interfere with the analysis itself or cause erroneous results due to inaccurate volumetric withdrawals. Applications where ambient temperature water is used for reagent preparation, but the tests are performed at elevated temperatures, are candidates for outgassing effects. If outgassing could interfere with test performance, including, chromatographic flow, colorimetric, or photometric measurements, or volumetric accuracy, then Deaerated Water
should probably be used, whether called for in the analysis or not. The above deaeration approaches might not render the water gas-free. At best, they reduce the dissolved gas concentrations so that outgassing caused by temperature changes is not likely.
Recently Boiled Water
This water may include recently or freshly boiled water (with or without mention of cooling in the title), but cooling prior to use is clearly intended. Occasionally it is necessary to use when hot. Recently Boiled Water is specified because it is used in a pH-related test or carbonate-sensitive reagent, in an oxygen-sensitive test or reagent, or in a test where outgassing could interfere with the analysis, such as specific gravity or an appearance test.