Elemental Analysis (incl. Heavy Metals) ICP Testing Utilizing ICP-MS
ICP or Inductively Coupled Plasma testing is an analytical technique used to measure and identify elements ranging from trace levels to higher concentrations in raw materials, finished products, excipients, API (Active Pharmaceutical Ingredients), water, and others whether the materials are organic or non-organic, aqueous, or non-aqueous. This elemental analysis which includes heavy metals testing, is critical for ensuring product quality, safety, and compliance with regulatory standards. Testing by ICP-MS was enforced by the USP (United States Pharmacopeia) as of January 1, 2018, when general wet chemistry was deemed to no longer be a viable method. NJ Labs is experienced and skilled in ICP-MS metals assays & elemental analyses and we will work with you to meet your testing requirements.
Inductive Coupled Plasma Mass Spectroscopy (ICP-MS)
ICP-MS is an acronym for Inductive Coupled Plasma Mass Spectroscopy. ICP-MS is an analytical instrument that combines inductive coupled plasma technology with mass spectroscopy for elemental analysis by generation of ions.
It combines a high temperature Inductively Coupled Plasma (ICP-MS) source with a mass spectrometer (MS). The ICP source converts the atoms of the elements in the sample to ions that are separated and detected by mass spectrometer. The ICP-MS combines multi-element capabilities with detection limits equivalent or below that of GFAA and can obtain isotopic information. The instrument can detect metals at parts per billion (ppb) and parts per trillion (ppt) levels.
ICP-MS is a high-tech addition to elemental analysis that can replace more conventional instrumentation, such as atomic absorption, which has been around for many years, and is not very sensitive. However, given the sensitivity and reliability of ICP-MS testing, the FDA has been recommending it more frequently. Companies requiring ICP-MS testing must often create an ICP-MS protocol for a method and submit the protocol along with the product to a laboratory. However, at New Jersey Laboratories, we specialize in developing and validating custom methods for your products according to your specifications, and then creating and writing ICP-MS protocols for you. We write comprehensive protocols which have satisfied regulatory requirements and we work closely with our clients during the entirety of the project, which includes explaining our process every step of the way. Our reporting process is detailed, complete and designed to withstand FDA scrutiny.
What can ICP-MS detect?
ICP-MS can detect nearly all elements in the periodic table, including metals, non-metals, and metalloids. Here are some of the key categories of elements that ICP-MS can detect:
- ICP-MS is particularly effective at detecting and quantifying various metals, including:
- Transition metals: e.g., iron, copper, zinc, chromium, nickel, etc.
- Alkaline earth metals: e.g., calcium, magnesium, strontium, barium, etc.
- Alkali metals: e.g., sodium, potassium, lithium, etc.
- Heavy metals: e.g., lead, mercury, cadmium, arsenic, etc.
- Rare Earth Elements (REEs):
- A group of 17 elements in the periodic table, including lanthanides (e.g., lanthanum, neodymium, europium) and yttrium.
- While ICP-MS is primarily used for metals, it can also detect and quantify certain non-metals such as phosphorus, sulfur, selenium, and others.
- Elements that have properties intermediate between metals and non-metals, such as arsenic, antimony, and tellurium.
- Isotopes and Radioisotopes:
- ICP-MS can differentiate between isotopes of the same element, allowing for precise determination of isotopic ratios and analysis of radioactive isotopes.
- USP General Chapter <232> – Elemental Impurities—Limits: USP General Chapter <232> outlines the permissible limits for various elemental impurities in drug products and ingredients. Although heavily used for the pharmaceutical industry, this chapter is applicable to other industries as well. It provides guidelines on the maximum allowable levels of specified elemental impurities based on the intended daily dose and the potential toxicity of the elements. The limits are expressed in parts per million (ppm) or micrograms per gram (µg/g) of the drug product or ingredient.
- USP General Chapter <233> – Elemental Impurities—Procedures: USP General Chapter <233> complements General Chapter <232> by providing detailed procedures and analytical methods for determining elemental impurities in pharmaceutical products. It describes the techniques and methods, including sample preparation, instrumental analysis, and validation requirements necessary to conduct elemental analysis to ensure compliance with the limits outlined in General Chapter <232>.
ICP-MS provides extremely low detection limits, often in the parts per billion (ppb) or even the parts per trillion (ppt) range, making it suitable for trace and ultra-trace analysis of elements in a wide range of sample types, including pharmaceuticals, cosmetics, nutraceuticals, food & beverage analysis, and clinical research.
Elemental Impurities Testing Utilizing USP General Chapters <232> and <233>
USP General Chapters <232> and <233> are specific chapters within the United States Pharmacopeia (USP) that provide guidelines and standards for elemental impurities in pharmaceuticals and supplements. NJ Labs performs compliance testing for elemental impurities based on these chapters to ensure the safety and quality of all products.
Compliance with USP General Chapter<232> and <233> is a critical aspect of pharmaceutical quality control and assurance. Together, these chapters establish a framework for assessing and controlling elemental impurities to safeguard patient safety and product quality. Manufacturers and regulatory agencies use these guidelines to perform elemental analysis and validate compliance with the specified limits for elemental impurities in pharmaceuticals. Their implementation is essential for regulatory compliance and helps ensure that pharmaceutical products do not contain harmful levels of elemental impurities such as heavy metals like lead, mercury, cadmium, and arsenic, which could pose health risks to consumers.
ICP-MS Frequently Asked Questions
How are samples prepared?
This depends upon the sample. While some water-soluble samples may not require digestion, most samples must be digested in a minimal acid solution that preserves the sample’s volatile elements. However, when we do digest samples, we use microwave digestion which dissolves the sample to extract metals in the sample.
How should samples be submitted for elemental analysis by ICP-MS when custom method development is needed?
In this case, the best way to submit samples is in two separate clean plastic containers – one for method development and one for validation. The sample size depends on the specifications and requirements.
What information must be submitted along with the sample?
A project’s elements, specifications, and any other special instructions must be submitted via email or attachments. Since elemental analysis by ICP-MS is not routine but a customized process, please contact us to discuss your project’s needs before submitting any information.
What is validation and what does this process entail?
Validation is the process that ensures the reliability, accuracy, and precision of the analytical results for the elements being analyzed in various sample matrices. It is a crucial step in ensuring the quality and reproducibility of the analytical data generated through the ICP-MS instrument.
The validation process entails:
- Accuracy and/or Precision: Validation verifies that the ICP-MS method can accurately determine the concentration of elements in a sample as well as provide precise and repeatable results.
- Assessment of Analytical Performance: Including parameters such as accuracy, precision, linearity, sensitivity, detection, and quantification limits as well as selectivity of the ICP-MS method.
- Calibration and Quality Control: To relate instrument response to known concentrations of standard solutions to ensure the instrument is properly calibrated while quality control samples are used to monitor and validate the accuracy and reliability of the test results.
- Matrix Interference Evaluation: Assesses potential interferences from the sample matrix that could affect the accuracy of the results.
- Reproducibility: To ensure that the method is reproducible across different instruments, analysts, and laboratories, leading to consistent and reliable results.
- Compliance with Regulations: Validating the method ensures the process complies with regulatory requirements and standards.
- Quality Assurance: Validation forms a critical component of a quality assurance program, providing confidence in the accuracy and reliability of the data generated for client samples.
In summary, the validation process in ICP-MS testing involves several steps, including setting acceptance criteria, conducting precision and accuracy studies, evaluating linearity and sensitivity, assessing detection and quantification limits, and demonstrating method robustness.
What samples must be validated?
Because the USP has not established specific methods, all samples should be validated to be fully compliant. When validation is not performed, accuracy, specificity and precision are not guaranteed, therefore the results may be categorized as non-GMP compliant analysis.
What validations does NJ Laboratories offer that are USP compliant?
- Limit Validation: The components of limit validation include but are not limited to detectability, linearity, precision for instrument methods (repeatability) and specificity. Limit validation allows us to report whether each element of interest passes or fails, as well as the specification pass/fail level. All results obtained above or below the specification are estimated.
- Quantitative Validation: The components required to satisfy quantitative validation include accuracy, precision, specificity, limit of quantitation, range, and linearity. The last three components are demonstrated by meeting the accuracy requirement. Accuracy is performed by spiking and recovering at 50%, 100% and 150% of the target of each element. Not all elements can be analyzed together due to interferences and several sequences may need to be performed to obtain all required results.
What is the validation procedure?
Once we receive the sample and all required information, our Quality Assurance department will write a protocol specific for the sample based on the provided specifications. The client must approve the protocol before the validation project can be scheduled. Once the validation is completed, our Quality Assurance department will review the data and write a validation report. Once the client approves the validation report, a product-specific Standard Operating Procedure (SOP) is written and takes effect for quality control (QC) analyses. Since the chemists who perform the validation also perform the QC analyses, no additional training is required, and our SOP can become effective upon approval.
How long does a validation take to complete?
Depending on the elements required, the nature of the sample, specifications, and method development, validation of a single sample can take 3-6 weeks.
Is ICP-MS equivalent to Atomic Absorption?
ICP-MS is a more advanced instrument compared to Atomic Absorption in terms of detection limits, precision, sensitivity, working range, sample throughput, data quality, reducing interferences, and ease of use. ICP-MS is also a multi-element instrument which allows us to test for several elements. Atomic Absorption on the other hand, is a single element instrument.