Pharmacopoeia reflects on permissible pharmaceutical impurities in parts per million limits

Abstract

PAT (Process Analytical Technology) produces enormous amount of inorganic impurities during unit operation. Inorganic impurities are mostly ionic matters which are water soluble cations & anions. Cations are iron (Fe²⁺/Fe³⁺), arsenic (As³⁺/As⁵⁺), lead (Pb²⁺) and anions are chloride (Cl^-), sulfate (SO₄^2-). All heavy metal impurities are cumulative poison which has affinity to bind with lipid layer to produce health hazards. Pharmacopoeia says about permissible limit of each ion in parts per million (ppm) level which is acceptable by the living body with no harmful effect. This is checked by limit test which is quantitative or semi-quantitative analysis to identify the permissible impurity which is below the adverse effect. The test is generally performed by turbidity/opalescence comparison test, color comparison test and stain comparison test between test sample and standard sample. If the intensity of turbidity/colour/stain of test sample is equal to or less than standard sample then the sample passes the limit test, if the intensity of turbidity/color/stain of test sample is greater than standard sample then the sample fails to pass the limit test.

Keywords: ppm, ppb, ppt, ppq, cations, anions, heavy metals, test solution, standard solution, turbidity, color, stain, organic impurities, inorganic impurities, residual solvents, class-I/II/III solvents, ICH guidelines, API, USFDA