Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) is capable of detecting metals at very low concentrations, as low as 1 ppq (one part per quadrillion). An ICP-MS unit ionizes the sample using inductively coupled plasma which is plasma which is argon gas heated to 10,000 °C causing the argon gas to increase in its electrical conductive properties and eventually transforming the argon from a gas state into the plasma state. Once ionized the molecules that make up the sample are separated based on it’s mass-to-charge ratio and quantified using a mass spectrometer.
There are a wide range of applications for ICP-MS, from geology to toxicology. In the pharmaceutical realm there are two general reasons for quantitating amounts of heavy metals, to identify contaminants and to perform bioanalysis on therapeutics designed to contain heavy metals.
Performing Heavy Metal Analysis For Pharmaceuticals
Heavy metal contamination in drug products could occur from many different sources. The following ways are common sources of heavy metal contamination:
– Residual catalysts that were intentionally add during production
– Metal contaminants from Processing equipment
– Raw materials contaminated with trace metals
– Contaminants could enter the product via container closure systems
Cancer therapies can also contain heavy metals. Arsenic, antimony, gold, vanadium, iron and other heavy metals are commonly used as chemotherapy agents. The bioanalysis of pharmacokinetic studies often use ICP-MS to track how the therapeutic is processed by in a living organism.
Heavy Metal Limits in Pharmaceuticals
All impurities of drug products should be controlled and shown to be within acceptable limits. The FDA, USP and ICH organizations have put forth guidelines to protect patients form the risks associated with heavy metal contaminants. The guidelines put forth are:
– USP <232>, Elemental Impurities – Limits
– USP <233>, Elemental Impurities – Procedures
– ICH Q3D, Guideline for Elemental Impurities
The FDA has also published a draft guidance titled Elemental Impurities in Drug Products. In this draft guidance the FDA encouraged the adoption of ICH Q3D and the two USP chapters, <232> and <233>. As of January 1st, 2018, the FDA required the compliance to these guidelines. The following was taken from the FDA website describing this new policy:
- All new and existing NDAs and ANDAs for drug products with an official USP monograph are required to meet the requirements in USP General Chapters <232> and <233> for the control of elemental impurities.
- Applicants submitting NDAs and ANDAs for drug products without a USP monograph are expected to follow the recommendations in the ICH Q3D Elemental Impurities guideline.
ICP-MS Testing at PBL
PBL has performed many R&D, cGMP and GLP ICP-MS studies on pharmaceuticals including bioanalysis studies to support the clinical trials of chemotherapy products. Please visit our ICP-MS testing page to learn more.