Determination of Metals

Dr. Mohammad A. Khanfar

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.

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.

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+

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

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.

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.

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.

Iron determination

• 4) Low concentration of Fe3+ are determined spectrophotometrically:

• Fe3+ + HClO4, absorbance at 240nm.

• Fe3+ + SCN-, brown color. • Fe2+ can be determined by 1,10-phenanthrolin:

Ferroin, red color

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

Calcium Determination

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

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

Cupper determination

• Assayed by iodometric method.

• Then back titrated with sodium thiosulfate

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