Potentiometric determination of calcium content with combined Cu ISE and reference Ag/AgCl electrode in API

There are numerous methods for determination of metal ions and other inorganic species in API. In the last years, there have been cases of hypercalcemia as conditions from a long-term medical therapy. From here goes the interest for better controlling of their intake with API that contain the metal ions in their composition. Because of its importance and uses in all areas of a human body (nervous system, muscles, heart and bone), a complexometric potentiometric method is suggested and tested for determination of Ca ions. Calcium content in analyzed in Atorvastatin Calcium x 3H2O, an API. Atorvastatin Ca x 3H2O is the calcium salt of atorvastatin, used as a synthetic lipidlowering agent. The calcium content of the active component has limits from 3.2% to 3.8% (on anhydrous and solvent free basis). The titration proposed for this determination is performed using combined Cu ISE and reference Ag/AgCl electrode. The method is based, on a complexometric titration with 0.1M EDTA as a volumetric solution, which forms a complex with calcium ions. The purpose of this determination was implementing potentiometric method in our laboratories.


Introduction
There are numerous methods for determination of metal ions and other inorganic species in API. In the last years, there have been cases of hypercalcemia as conditions from a long-term medical therapy. From here goes the interest for better controlling of their intake with API that contain the metal ions in their composition. Because of its importance and uses in all areas of a human body (nervous system, muscles, heart and bone), a complexometric potentiometric method is suggested and tested for determination of Ca ions.
Calcium content in analyzed in Atorvastatin Calcium x 3H 2 O, an API. Atorvastatin Ca x 3H 2 O is the calcium salt of atorvastatin, used as a synthetic lipidlowering agent. The calcium content of the active component has limits from 3.2% to 3.8% (on anhydrous and solvent free basis).
The titration proposed for this determination is performed using combined Cu ISE and reference Ag/AgCl electrode. The method is based, on a complexometric titration with 0.1M EDTA as a volumetric solution, which forms a complex with calcium ions.
The purpose of this determination was implementing potentiometric method in our laboratories. Potentiometer Metrohm 888 Titrando instrument with Tiamo software and 0.1M EDTA burette was used for the potentiometric titration and analytical balance Mettler Tolledo was used for weighting the samples. The samples were dried in laboratory Oven Binder. The titration was performed using Metrohm 6.0502.140 Cu ISE with 6.0733.100 reference electrode (Ag/AgCl).

Procedures for Ca determination
Factorization of 0.1M solution EDTA From the chelometric-dried standard, three samples (around 100mg) were prepared in 100 mL glass beaker. Magnetic stirrers were used for dissolving the standard with 10 mL distilled water and 3 mL 1N HCl. After that, 40 mL water was added and mixed well. Then, 5 mL of the prepared Buffer and 1 mL of CuEDTA complex were added. This formula was used for calculations: The parameters of the method were as follows: -Mode -MET U; -EP Criterion -20mV (for titer and for sample), for blank titer 10mV ; -EP recognition -Greatest; -Stirring rate -4; -Volume increment for sample and for the blank -0.1mL sample and 0.002mL, respectively; -minimum waiting time -10 s; -maximum waiting time -20 s; -signal drift -20 mV (for sample and for blank), 40mV (titer); The parameters of method are adjustable, depending of the type of instrument used for titration.

Results and discussion
Titer determination and potentiometric determination of Ca was performed several times. Part of the results are presented: -For titer determination an average value is used from three measured samples (m1 = 97.48 mg, m 2 = 97.54 mg and m 3 = 97.51 mg).
-The weights for the samples prepared are m 1 = 500.05 mg and m 2 = 500.34 mg. The volume consumed for determination is: Blank (V titer ) = 0 mL Sample 1 (V titer ) = 4.1204 mL Sample 2 (V titer ) = 4.1269 mL With the formula for Ca content, the potentiometric method gave us results for the two samples prepared, 3.31% from the titration and 3.46% calculated on solvent free and anhydrous basis.
All calculations were performed using Tiamo software on the potentiometer.