Facet Analytical Services and Technology LLC

Solid Dose Calibrator for Karl Fischer Titrations
W.A. Young, Facet Analytical Services and Technology, LLC
Bioanalytical Systems, Inc. / August 2005

Originally published in Current Separations (Vol. 21 No. 2) | View entire article and results (PDF)


FASTRATE™ unit dose packaging, CofA, and PI

Moisture content determination is an important measurement for agricultural, petroleum, pharmaceutical, plastics, cosmetics, and foodstuff industries. The Karl Fischer titration is a widely-used method for this determination (1). Volumetric Karl Fischer titrations typically use certified water samples for calibration prior to analyses.

However, these calibrations can be cumbersome, requiring a syringe or a weigh boat to dispense the standard. Depending upon the skill of the analyst, this can lead to assay variability due to uncontrolled ingress of external moisture or residual standard unaccounted for during transfer to the vessel. Automation of these processes would also be costly and require extensive administrative control.

However, a water standard in tablet form (Fastrate™ Volumetric) is now available as an alternative for titrator calibration. The moisture content of these tablets can be varied according to the application (F1), and is determined for each lot of tablets by in-process testing, the results of which are reported on a certificate of analysis. Since delivery of a tablet is simpler than delivery of a bulk powder or delivery using a syringe, use of a tablet should eliminate the possibility of residual standard and should also shorten the transfer time, thereby reducing ingress of external moisture. Therefore, the assay variability should be reduced. Tablets can also be used as a check standard throughout a run, and could also facilitate complete automation of the measurement, since the delivery mechanism is the same for both standard and sample.

Assay parameters dictate required water content that must conform to pharmacopeial standards, F1

In this study, moisture content determination was performed on Fastrate™ 10mg Volumetric tablets, and the results compared with those obtained using two other standards, one requiring a bulk powder, the other a syringe. The times required for each of the sample preparation and transfer steps were also compared.


Titrations were performed using commercial analytical instrumentation and a one-component reagent system. Instrument calibration was performed per Standard Operating Procedure (SOP) using purchased standards of known water content.


Approximately 80 mL of solvent is required to completely submerge the electrode. The working medium is added to the titration vessel and conditioned to equilibrium (end point) with Karl Fischer reagent. The weighed standard/sample is transferred to the vessel and titrated to the same end point. The volume of reagent required to reach the end point is determined by the moisture content of the sample. This volume is influenced by titer stability, analyst technique, and ambient conditions (e.g., humidity) and determines the reagent strength factor of the titer during instrument calibration. Standards of theoretical water contact are titrated to the end point as described above until a mean value of < 1.0% Coefficient of Variation (CV) for a predetermined number of replicates (n=3) has been achieved.

Moisture content determination using volumetric Karl Fischer titration was performed on Fastrate™ Volumetric and two leading conventional standards after instrument calibration was complete (T1).

Comparitor analysis, T1

One standard (C1) required injection using a syringe, and the other (C2) used a bulk powder. Each replicate of Fastrate™ Volumetric was bracketed by replicates of C1 and C2 in a group (F2 and F3).

Sample preparation and transfer times for each replicate, F2

Water Content versus Replicate Analysis, F3

Six groups were analyzed and a single instrument was used to perform all analyses on the same day. During analysis, sample preparation, transfer and exposure times were recorded for each replicate. The working medium was replaced and reconditioned to equilibrium following completion of three consecutive titrations. All analyses were completed under the same instrument calibration.


View entire article and results (PDF)
Results are located on page 3 in the Special Interest section

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