Inadequate inductively coupled plasma (ICP) sample preparation or improper configuration of the sample introduction system can have negative effects such as signal drift, increased background, insufficient detection limits, or unexpected interferences. This article will focus on the key steps required to create a sample preparation workflow for elemental analysis.
ICP-MS is mainly used to analyze liquid samples.
In most cases, the sample must (if possible) be dissolved in a suitable diluent. While aqueous diluents such as ultrapure water or dilute acids are generally easier to handle, organic solvents may be able to handle elemental impurities in some active pharmaceutical ingredients. If the sample cannot be dissolved immediately, it needs to be assisted by heating methods, such as melting (such as lithium metaborate) or microwave digestion are common methods. However, all of the above methods have common disadvantages, such as digestion time, reagent cost, and digester hardware requirements. Additionally, insufficient cleaning of crucibles or digestion vessels between reagents or samples used for digestion can be a problem.
Regardless of the digestion method used, a clear and particle-free solution is the ideal result for digestion. But before putting the digest on the machine, it is important to consider some parameters. The amount of total dissolved solids (TDS) is calculated by dividing the weighed amount by the final volume of the solution after digestion. The maximum working range of TDS is different between ICP-OES and ICP-MS, which we describe later. Digestion residual acid or acid mixture concentration will not only affect the performance of the instrument, but also affect the configuration of the sampling system. For example, if there is a high concentration of hydrofluoric acid (HF) in the digestion solution, it is necessary to replace the quartz material sampling component to ensure its inertization. Ideally, the residual acid concentration in the digest should be below 5% (v/v).
Direct analysis of solid samples can be used as an alternative in some cases, such as conductive samples (metals and semiconductors), non-conductive samples (mineral particles, paper and plastics), and biological materials (tissue sections). Using a laser system focused directly on the sample surface, short pulses of high-intensity light can convert solid samples directly into aerosols, which are transported to the ICP for analysis. Laser ablation (LA) enables direct sampling of a range of solid materials without the use of hazardous chemicals and minimizes the possibility of pre-treatment contamination. Due to the typical small spot size around 200 μm, laser ablation is considered quasi-nondestructive and thus can be an alternative for analyzing valuable samples. However, sample uniformity can be an issue when using LA-ICP-MS to determine concentrations in bulk materials, thus requiring careful selection of the sample area. On the other hand, LA-ICP-MS can also obtain information about the lateral distribution of analytes in the sample, which is beneficial for characterizing geological or biological samples.
Acid and container cleanliness
ICP-MS is a technique for the analysis of trace and even ultra-trace elemental impurities, so the background of the target analytes must be as low as possible. Otherwise, false positive results and insufficient detection limits could lead to extensive follow-up in routine laboratories. For some elements, such as rare earth elements, natural abundance in the environment is low, so background contamination may not be found in water, acids, or sample vials used during sample preparation. Other elements, especially alkalis, alkaline earths and transition metals such as sodium, potassium, iron, copper or zinc, may leach significantly from plastic utensils such as bottles and caps. Preliminary leach testing of vial purity is therefore strongly recommended when changing between batches or brands. Low purity acids may also increase elemental background in the analysis.
Acids and other reagents commonly used for elemental analysis, such as nitric acid, hydrochloric acid, and hydrogen peroxide, are available in varying degrees of purity, but for ultratrace analysis using ICP-MS, the highest purity reagents should be used. As an alternative, subboiling distillation can be used to purify low-purity acids, which is a cost-effective way to improve acid purity. Another potential contamination factor could be the water used to prepare the diluent solution. Regular checking of trace elements and regular maintenance of the pure water system (according to the manufacturer’s recommendations) are highly recommended. For trace element analysis, it is recommended to use water with a resistivity of 18.2 MΩ cm whenever possible.
Microwave digestion is commonly used in many sample preparations because microwave digestion helps break down difficult matrix materials and enables digestion to be run at high temperatures and pressures. However, the choice of an appropriate acid is still crucial, and in many cases efficient digestion often requires a combination of different acids or oxidizing agents. Using an acid mixture also immediately stabilizes some elements in solution.
Nitric acid (HNO 3) is commonly used as a diluent for elemental analysis. Hydrogen peroxide (H 2O 2) can effectively decompose most organic substrates (such as food, feed). As an alternative, perchloric acid can be used to increase the oxidation potential of acid mixtures, but with extreme care, perchloric acid reacts strongly and rapidly with organic matrices. Adding an appropriate amount of hydrochloric acid (HCl) is beneficial to unlock and stabilize certain inorganic materials. For example, aqua regia (3:1 mixture of hydrochloric acid and nitric acid) can effectively dissolve metallic materials. Hydrochloric acid also helps to stabilize the digestion of key contaminants in the sample, such as mercury and platinum group metals. It is important to ensure that the concentration of HCl is high enough (2% or even higher) so that the initially formed precipitate (HgCl or HgCl 2) is converted to a soluble chlorine complex (HgCl 42-).
Sulfuric acid (H 2SO 4) is beneficial for digesting certain sample types on hot plates and some types of high pressure digestion systems, but this acid should never be used in the microwave with Teflon containers because Teflon is at the boiling point of sulfuric acid melting at temperature. Additionally, sulfuric acid produces additional sulfur-based spectral interferences in ICP-MS and is therefore used only when no alternative is available.
For any of the above situations, always wear proper personal protective equipment when handling acids and other hazardous chemicals. Detailed guidance on the correct acid or acid mixture, sample and acid volumes to weigh and add, and temperature program can be obtained from the manufacturer of laboratory microwave digesters.
Smartly dilute samples
Samples with high TDS content can cause ICP-MS signal suppression and drift. The typical upper limit of TDS content in ICP-MS is between 0.2% and 0.5% (m/v). Special accessories at the front end of ICP-MS, such as dilution with argon, can directly introduce a solution with a high TDS content, with a concentration exceeding 3% to 4%, but this method is still dilution, which ultimately reduces sensitivity. The biggest advantage of this accessory is that it can save the manual dilution step in the pre-treatment, thus saving the operator’s time, reducing the cost and waste of diluent solution, preventing contamination and avoiding human errors. However, since the diluent changes the ICP conditions, it is necessary to fix the dilution factor for all standards and samples in the batch. For batches containing different sample types, this limited flexibility becomes a disadvantage, as lower matrix samples will be over-diluted by setting the dilution factor to be able to measure higher matrix samples, resulting in a method detection limit (MDL) degrades and reduces the accuracy of analyzing these samples.
As mentioned earlier, it is important to be aware of potential background from laboratory equipment and chemicals (contamination) or other samples (carryover or cross-contamination). The former can only be identified through rigorous testing of all equipment and different batches of chemicals, while the latter requires an effective cleaning strategy in place between runs. For samples that require digestion prior to analysis, a method blank should be prepared for each batch of samples, including all steps and reagents used in the process, but excluding the samples. In this way, any potential contamination during the digestion step can be identified, traced back to its source and corrected where possible, before troubleshooting or even reporting on potentially skewed results. Table 1 outlines common reasons why the analysis may be biased by contamination or carryover cross-contamination.
Identifying Mass Spectrometry Interferences
Usually due to limited sample information, it is not immediately possible to identify whether it is a mass spectral interference. Sometimes other matrix elements that do not need to be quantified in the sample will cause a series of difficulties. These difficulties are often identified when the sample is analyzed. First, matrix interferences cause confusing results. Second, subsequent samples may also be contaminated by carryover. Influence. In order to identify such potential challenges caused by unknown samples before they become confounding, it is recommended to follow a few simple steps.
To find matrix elements or challenging interferents, running a semi-quantitative scan can be a good way to characterize high matrix elements or indicate possible mass spectral interferences. Using slightly higher than usual dilution factors will protect the instrument from ongoing contamination. Oftentimes, encountering atypical mass spectral interferences can cause puzzling results. For example doubly charged ion interference. Doubly charged interferences from the rare earth elements neodymium (Nd), samarium (Sm) or gadolinium (Gd) interfere with arsenic ( 150Nd 2++ and 150Sm 2+) and selenium ( 156,160Gd 2+), but ICP-QQQ can reliably remove these interferences. For example, 206Pb 2++ may affect 103Rh+if the lead content in the sample is high. In this case, the interference does not bias the sample itself, but indirectly causes problems with the internal standard response.
Summarize
A critical study of all steps in a sample preparation protocol is necessary to ensure successful, accurate and reliable determination of trace elements. By evaluating all consumables and reagents, and preparing appropriate method blanks and quality control (QC) checks, it helps to identify and rule out potentially biased results.