I work in a GMP regulated laboratory and we purchase NIST traceable volumetric solutions for our titrations. We traditionally use the CofA value for the normality for the calculations instead of standardizing the solutions ourselves. This has not been an issue until recently but now my management is questioning this practice.
I am wondering if others out there periodically confirm the normality of solutions that have been purchased as traceable to NIST, or if the titrants are used as received? And if we standardize NaOH v. potassium hydrogen phthalate, then we place our trust in that standard.
And if you do check your titrants, how often? Every time used, or every time if not within 3 months, etc. Thanks.
And just titrants used to assay APIs? What about titrants used to assay incoming raw materials using non-validated procedures?
I’m looking for what the industry practice is. Below is the intro from USP regarding volumetric solutions in the reagent chapter:
Preparation and Methods of Standardization of Volumetric Solutions
The following directions give only one method for standardization, but other methods of standardization, capable of yielding at least the same degree of accuracy, may be used. The values obtained in the standardization of volumetric solutions are valid for all Pharmacopeial uses of these solutions, regardless of the instrumental or chemical indicators employed in the individual monographs. Where the apparent normality or molarity of a titrant depends upon the special conditions of its use, the individual monograph sets forth the directions for standardizing the reagent in the specified context. For those salts that usually are available as certified primary standards, or that are available as highly purified salts of primary standard quality, it is permissible to prepare solutions by accurately weighing a suitable quantity of the salt and dissolving it to produce a specific volume of solution of known concentration. Acetic, hydrochloric, and sulfuric acids may be standardized against a sodium hydroxide solution that recently has been standardized against a certified primary standard. All volumetric solutions, if practicable, are to be prepared, standardized, and used at the standard temperature of 25. If a titration is carried out with the volumetric solution at a markedly different temperature, standardize the volumetric solution used as the titrant at that different temperature, or make a suitable temperature correction.
Where does this come from, “best industry practice”, and 15 days. Or 15 working days?
I notice in the USP Volumetric Solutions sections, that it’s “REAL” helpful, with terms like “standardize frequently” and not detailing any more, and not even indicating whether a standardization (say: sodium hydroxide) needs to be done in duplicate, triplicate, etc. The way it reads to me is that singleton is acceptable, or is USP trying to conserve ink?
And the FDA/USP wonders why people are confused by this stuff…
when FDA or other agencies do not specifies clearly about a study. we need to establish the acceptance criteria by assessing risk .
Best industry practice means, Many industries studies the stability of these solutions and validity is assigned and this information is shared and harmonised. Then it becomes best practice when FDA or other agencies do not specifies clearly about this.
For every best practice, There needs a proof and experience that gives robust and accuracy.
I have an approach, if you find useful, you can use that.
Prepare the Volumetric solution and standardize that with the given procedure.
Validate the time period for “how many days that solution is useful”. I mean to say that check the molarity or Normality of that solution regularly, until it gets failed. Eg: days 1,2,3,4,5,6,7,8,9,10,11,12 etc…
Then determine the number of days that volumetric solution is giving the correct Normality or Molarity.
Say for example 10 Days, then you make the Stability of that solution to 8 days.[Apx value]
So the Volumetric solution life is validated.
Prepare the Protocol and report the results. You can use this in Audits also.