United States Pharmacopeia (USP) Chapters 232 & 233.

Traces of metals that can be found in finished products are referred to as elemental impurities. The presence of these impurities can occur from active pharmaceutical ingredients (APIs), bulking agents (stabilisers, binders, colours, flavours, coatings and so on), metal catalysts, reagents used during synthesis and the process vessels used in manufacturing. This can cause many concerns from the effectiveness of a drug, to a product becoming toxic for ingestion and causing side effects. The shelf life of a product could also be affected. Here is when the analysis of these elemental impurities becomes vital in monitoring and controlling the presence of trace metals. Many industries can be affected by this, pharmaceutical, cosmetic, food and drink, to name a few.

Elemental ImpuritiesUnited States Pharmacopeia (USP) chapters 232 Elemental Impurities-Limits and 233 Elemental Impurities-Procedures state limits and guidelines for monitoring a number of metal elemental impurities in products using inductively coupled plasma (ICP) optical emission spectroscopy (ICP-OES) or mass spectrometry (ICP-MS). A list of 24 elements has been given with their known toxicity limits in μg/day, Ag, As, Au, Ba, Cd, Co, Cr, Cu, Hg, Ir, Li, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru, Sb, Se, Sn, Tl, and V.

 

Table below: Permitted Daily Exposures for Elemental Impurities. Refer to “USP Chapters and Implementation Strategy” from U.S Food and Drug Administration. https://www.fda.gov/

Element Oral PDE (µg/day) Parenteral PDE (µg/day)
Ag 150 10
As 15 15
Au 100 100
Ba 1400 700
Cd 5 2
Co 50 5
Cr 11000 1100
Cu 3000 300
Hg 30 3
Ir 100 10
Li 550 250
Mo 3000 1500
Ni 200 20
Pb 5 5
Pd 100 10
Pt 100 10
Os 100 10
Rh 100 10
Ru 100 10
Sb 1200 90
Se 150 80
Sn 6000 600
Tl 8 8
V 100 10
Table below: Permitted Concentrations of Elemental Impurities for Individual Component Option. Refer to “USP Chapters and Implementation Strategy” from U.S Food and Drug Administration. https://www.fda.gov/

Element Oral Concentration (µg/g) Parenteral Concentration (µg/g)
Ag 15 1
As 1.5 1.5
Au 10 10
Ba 140 70
Cd 0.5 0.2
Co 5 0.5
Cr 1100 110
Cu 300 30
Hg 5 0.5
Ir 10 1
Li 55 25
Mo 300 150
Ni 20 2
Pb 0.5 0.5
Pd 10 1
Pt 10 1
Os 10 1
Rh 10 1
Ru 10 1
Sb 120 9
Se 15 8
Sn 600 60
Tl 0.8 0.8
V 10 1

 

At Exeter Analytical we demonstrate correspondence to USP 232 and 233. Our Dual ICP-OES system is combined with a high-resolution echelle spectrometer and a charge injection device (CID) detector which produces higher sensitivity and lower noise. This allows us to achieve maximum sensitivity when analysing samples in USP limits. Our detection limits can go down to less than 1ppm in sample and our instrument allows us to detect down to 10ppb. All our samples are routinely run at multiple wavelengths to identify any potential interference that could affect our data quality.