1. Determination of Metals
Dr. Mohammad A. Khanfar

2. Metals
Metals can be either impurities or the active ingredient in pharmaceutical preparations.
If present as impurities (traces), then physical methods are used for their determination. Such as:
1) Visible absorption spectroscopy of metal-ligand complexes.
2) Atomic absorption spectroscopy.
3) Emission spectroscopy.
If the metal is the active ingredient it is usually present in high level, so it’s determined by:
First the metal needs to be freed from the organic or inorganic (salt) form.
Determined by certain elemental analysis procedures.

3. Determination of Mercury
Organic and inorganic mercury may be used in pharmacy:
Mercuric chloride, phenyl mercuric benzoate are antiseptic.
Meralluride and mersalyl are diuretics.
Sample preparation:
In pharmaceutical samples mercury is present as R-Hg-R`
First step is to free mercury by either:
1) Dissolving inorganic Hg in HNO3 to give Hg2+.
2) For organic mercury (where Hg is bound to carbon) mercury is freed either by oxidation to Hg2+ or reduction to Hg0 metal.

4. Determination of Mercury
Oxidation: the most common method is wet oxidation: mercury compound is refluxed with oxidizing mixture to give Hg2+.
Oxidizing agents such as: H2SO4/HNO3, or H2SO4/H2O2, or HNO3/KMnO4
Reduction: commonly done using Zinc (Zn) with acetic acid or in hydroxide solution (NaOH).
The product of reduction is excess Zn and Hg0 metal(known as zing amalgam).
After reducing Hg, the resulting amalgam is dissolved in HNO3/H2SO4 to fully oxidize Hg to Hg2+

5. Determination of Mercury
Determination of Hg2+
1) Thiocyanate titration: most popular method.
Titrant: SCN-
Analyste: Hg2+ in HNO3/H2SO4 (or HNO3 for inorganic)
Indicator: Ferric ion (Fe3+)
End point: brownish-red due to the formation of (FeSCN)2+
The reaction:
The reaction must be carried at 15Co to minimize the dissociation of Hg(SCN)2

6. Determination of Mercury
2) Colorimetric determination of Hg2+:
Under acidic condition, Hg2+ forms complex with dithiazone (colorful):
Acetic acid is added to stabilize the color.
The complex is extracted with chloroform and measured at 500nm.

7. Iron determination 1) Redox titration
Fe2+ ion is titrated with oxidizing agent (KMnO4, K2Cr2O7, Ce4+).
Mostly titration is direct.
If the sample contain both Fe2+ and Fe3+, the sample is first reduced by Zn to convert all Fe3+ to Fe2+ then determined as usual .
Fe3+ can be determined with I-:
I2 is then titrated with Na2S2O3.

8. Iron determination 2) Complexometric titration
Fe3+ form stable complexes with EDTA and thus can be determined compleximetrically.
3) Fe3+ can be determined gravimetrically by precipitation as Ferric oxinate.

9. Iron determination
4) Low concentration of Fe3+ are determined spectrophotometrically:
Fe HClO4, absorbance at 240nm.
Fe SCN-, brown color.
Fe2+ can be determined by 1,10-phenanthrolin:
Ferroin, red color

10. Calcium Determination
Two common methods:
1) ppt Ca2+ by oxalate, then Ca2+-oxalate is removed by filtration, dissolved in acidic medium and titrated with KMnO4.
Mg-oxalate is water soluble

11. Calcium Determination
2) The preferred assay of Ca2+ with EDTA
Indicator: best choice is hydroxynaphthol blue.

12. Lead determination
The test identifies the substance to be examined as a salt of lead, Pb2+
Lead will form a yellow insoluble salt with chromate
The ppt is then filtered and titrated with measured excess of NaOH.
And then back titrated with strong acid

13. Cupper determination Assayed by iodometric method.
Then back titrated with sodium thiosulfate

14. Zinc determination
In the first step of Zn determination, the test solution is added to strong NaOH solution. The zinc hydro complex is formed:
Then ammonium chloride solution is added to change hydro complex into a soluble ammonia complex, the tetramminezincate(II) ion
The last step is to add sodium sulfide solution, which causes the formation of a white flocculent precipitate of zinc sulfide, which determined gravimetrically