of Applications Complexometric Titrations
Complexometric Titrations are useful in a couple of different fields, namely analytical
chemistry and the pharmaceutical sciences. In analytical chemistry, there are direct, back,
replacement, and indirect titration methods depending on what is being titrated and the goal of
what concentration to determine. In the pharmaceutical sciences, complexometric titrations are
used to determine the amount of metals in different formulations and also to determine the
hardness of water.
Analytical Uses of Complexometric Titrations
1) Direct TitrationOf the analytical methods, this is the most simple. It involves the addition of EDTA to the
solution being titrated until the end point is achieved. As in acid-base titrations, the indicator for
this type of titration must show a clear color change in order to give successful and accurate
titration data. Previous to the titration, EDTA must be standardized, and sometimes additional
reagents need to be added to complete the titration. This method is successful for metals like Cu,
Mn, Ca, Ba, Zn, Cd, Al, Sn, Pb, and many others. One thing to be careful of in a direct
complexometric titration is the presence of other ions in solution, which could cause a change in
the results.
2) Back TitrationIn this method, an excess of EDTA titrant is added to the solution being titrated in order
to put all of the metal ions in the solution into the EDTA complex. The excess EDTA that does
not complex with the ions in the original solution is then titrated with a second metal ion. The
method is useful when the analyte precipitates without EDTA, reacts extremely slowly with the
titrant, or blocks the indicator. One concern with back titrations is making sure that the
standardized metal used in the back titration of the EDTA does not displace the analyte ion for
the complex.
Example: The titration of Mn cannot be done by direct titration because of the precipitate
Mn(OH)2. Using a back titration, the Mn can be treated with an excess of EDTA and then titrated
with a standard solution of Zn using the indicator Eriochrome black T as an indicator of the end
point.
3) Replacement TitrationThis method can be used when direct or back titrations have difficult to determine end
points or when there is not a proper indicator for the analyte. In this method, the analyte metal is
added to EDTA that is already complexed with another metal. metal The ion being analyzed
displaces the metal ion originally in the complex. Then the solution can be titrated with
standardized EDTA.
Example: The titration of Mn can also be done by replacement titration. In this situation, Mn is
added to an excess of Mg EDTA complex. Mn is able to displace Mg from the complex because
Mn forms a more stable complex with EDTA (this is necessary in order for the replacement to
work). The Mg released from the EDTA complex is what ends up being titrated by a standardized
EDTA solution using Eriochrome black T indicator. Ca, Pb, and Hg are examples of a few other
metals that can be titrated using this method.
4) Indirect Titration (Alkalimetric Titration)This method can be used on anions that form precipitates with metals and do not react
with EDTA. In this situation, the anion is added to a metal cation which forms a precipitate. This
precipitate is then washed with an excess of disodium EDTA solution to form a metal complex
with the metal cation. The protons displaced from the disodium EDTA when a heavy metal is
added can then be titrated with sodium alkali.
Example: The titration of barbiturates.
Pharmaceutical Applications of Complexometric Titrations
Using the analytical methods described above, many different pharmaceutical assays can be
completed in order to determine the amount/concentration of a metal in formulation. Below is a
list of some of the many different solutions, active ingredients, or excipients titrated by scientists
in the pharmaceutical sciences.
Ca, Mg, Pb, Zn, Al, Fe, Mn, Cr, etc.
Assay of CaCO3
Calcium Lactate Tablets
Calcium Lactate Injection
Calcium Gluconate
Calcium Gluconate Injection
Calcium Gluconate Tablet
One of the major titrations done by the pharmaceutical industry and scientists in the
pharmaceutical field is a titration for the determination of the Hardness of Water. This is caused
by the presence of Ca and Mg in a water source and is expressed in the amount of Ca and Mg
ions in ppm. In this titration, amounts of Ca and Mg are determined concurrently, using a
standardized EDTA solution and Eriochrome black T as the indicator. As EDTA is added, the
Ca2+ are complexed first with the EDTA, and is excess EDTA is added the Mg ions complex with
the EDTA as well. The end point occurs when all of the Ca and Mg ions in solution are in
complex, allowing for the determination of the amount of ions in the water.