Elemental impurities affect drug effectiveness, it doesn’t have any therapeutic benefit but has a toxic effect on the patients. Elemental impurities may be present in drug products due to different sources such as catalysts, raw materials, excipients, equipment, or packing materials.
As per recent necessities, elemental impurities guidance of ICH Q3D, USP Chapters <232>, made effective shifting the old requirements for heavy metals. The limits are much lower for most toxic metals. The earlier heavy metal method was not specific and accurate for each one hence new testing procedure was applied by using sophisticated, costly, and sensitive technology such as inductively coupled plasma optical emission spectroscopy (ICP-OES) or inductively coupled plasma mass spectrometry (ICP-MS).
ICP is the abbreviation for inductively coupled plasma and is the method of optical emission spectrometry OES. ICP-OES is an analytical method that is used for the detection of chemical elements, which uses the emission spectra of a sample to quantify and identify the elements present, and the constituent elements are identified by the characteristic emission lines and further quantified by the intensities of the same lines. In ICP-OES there is the excitation of electrons of elements in an atmosphere which is termed plasma and it is the diffusion of light after electron release. It is one type of method of optical emission spectrometry and it uses inductively coupled plasma by which atoms and ions get excited and which emits electromagnetic radiation characteristic of a particular element at wavelengths, further the
principle of ICP-OES is that the atoms and ions absorb energy and the electron moves from the ground state to the excited state and the excited atoms release the light of specific wavelengths as when transitioning to a lower level. The source plasma is high temperature and often argon is an ionized source of gas. The plasma source has a temperature in the range of 6000 to 10000 K and has a very high electron density and the energy is used for (excitation-emission) of the sample. ICP-OES is a sensitive and moderately multi-element technique with a linear range and sensible detection range which is suitable over the concentration from ppm to ppb.
Difference between ICP-OES and ICP-MS
ICP-OES and ICP-MS are vital analytical techniques in the determination of trace elements analysis from drug substances and drug products. This article describes the difference between ICP-OES and ICP-MS.
|Cost||The cost of ICP-OES is less than ICP-MS but the operation cost is high due to the higher consumption of argon gas. Asper ICP-OES, photons have no mass, and no memory effects hence it’s a simple technique for use hence it requires less maintenance.||ICP-MS is more expensive because of its handling cost and it requires a cleanroom. It requires extra maintenance due to its spare parts. Argon gas consumption is similar.|
|Consumables||The main consumable supplies in ICP-OES are in the plasma torch and in the sample introduction area.||Consumables are placed inside the mass spectrometer which is, the sampler and skimmer cones and another main consumable is the detector.|
|Handling and Sample Preparation||Handling is usually easier to operate than ICP-MS. ICP-OES is exceptional for its speed, cost, and ease of sample analysis. It allows a relatively big amount of dissolved solids and is more matrix tolerant. In a single sample analysis, up to 60 elements can be screened within a minute. sample requirement is generally from 0.1g to 1.0g||Handling is easy but sample preparation is more crucial because it dissolved in 2% HNO3 v/v, a total dissolved solids content. It’s is having the benefit of determining much lower concentrations of elements present. Analysis of high total dissolved solids samples is unfit because cones of the interface can be blocked. Ideally the conc. restricted to 0.2% (2 g/L) of dissolved solids which requires dilution of samples.|
|Detection||It is a moderately sensitive multi-element technique with a dynamic linear range and sensible detection range suitable over concentrations from ppm to ppb. Isotope ratio can’t establish.||Exceptional sensitivity for a multi-element technique for trace analysis and for high precision isotope ratio studies. ICP-MS is capable of ultra-trace detection ranging from ppb to ppt.|
|Principal||In ICP-OES there is the excitation of electrons of several elements in an atmosphere termed plasma and the diffusion of light after electron release.||Inductively coupled plasma source converts elemental atoms into ions to sample and were isolated and detected by a mass spectrometer. Mass of elemental ions formed by high-temperature argon plasma measured by ICP-MS. Ions formed in the plasma are divided from the mass to the load, making it possible to detect and quantify unknown materials. MS then categories the ions according to their mass/charge ratio followed by leading them to an electron multiplier tube detector that identifies and quantifies each ion.|
|Method Development||Method development is quite easy.||Method development is significantly more difficult than for ICP-OES.|
|Grade of Chemicals||Analytical-grade chemicals, solvents, and reagents can be used for analysis.||It requires high-purity grade solvents, reagents, and chemicals.|
|Instrument Handling Expertise||Operation of ICP-OES and samples analysis were done by a normal analyst and calibration can be done by the expert analyst.||The operation of ICP-MS is done by a highly sophisticated instrument and it’s supervised by a highly skilled professional.|
Elemental impurity requirements are much more stringent than the past heavy metal. Due to the complex sample matrix and the stringent limits, analysis involve a more sensitive, precise, and accurate method of analysis. It requires highly sophisticated, sensitive, and expensive testing instruments and procedures.
This article describes the comparative difference between both techniques this information can be helpful to assess the usefulness of techniques as per requirement.
- ICH Q3D (R1) Guideline for Elemental Impurities,
- Elemental Impurities in Pharmaceuticals: Updates: USP Website: http://www.usp.org/chemical-medicines/elemental-impurities-updates,
- Approaches to Maximize Performance and Reduce the Frequency of Routine Maintenance in ICP-MS,” R. Brennan, J. Dulude, R.J Thomas, Spectroscopy,
- Measuring Elemental Impurities in Pharmaceuticals: A Practical Guide, Robert. J. Thomas; CRC Press, Boca Raton, FL, ISBN 9781138197961, February 2018,
- Choosing the Right Trace Element Technique: Do you know what to look for,” R.J. Thomas, Today Chemist at Work.