The Hidden Problem of Analyte Loss
Elemental analysis by ICP-OES and ICP-MS is only as reliable as the sample that reaches the plasma. For the majority of analytes, properly acidified solutions remain stable for months or even years, and standard digestion protocols deliver quantitative recoveries without incident. However, a subset of elements—those that form volatile compounds, adsorb onto container surfaces, or exist in unstable oxidation states—can be partially or completely lost before the sample is ever measured. When this happens, the instrument reports a number that is precise, reproducible, and wrong.
The elements most susceptible to these losses are well known to experienced analytical chemists: mercury (Hg), arsenic (As), selenium (Se), boron (B), sulfur (S), iodine (I), osmium (Os), and to a lesser degree antimony (Sb) and tin (Sn). Each presents its own combination of volatility, adsorption tendency, and chemical reactivity that must be managed through deliberate choices in digestion chemistry, temperature control, vessel selection, acid matrix, and storage conditions. Yet in many laboratories, sample preparation protocols are inherited rather than questioned, and the specific requirements of these difficult analytes are overlooked until recoveries fail or proficiency testing results raise questions.
This article provides a practical, mechanism-based guide to understanding and preventing analyte loss for volatile and semi-volatile elements. It draws on Inorganic Ventures’ extensive experience in sample preparation chemistry, chemical stability research, and certified reference material formulation to help laboratories build more robust workflows and generate defensible data for even the most challenging analytes.
Mechanisms of Analyte Loss: Understanding What Goes Wrong
Volatilization
Volatilization is the most direct and often the most catastrophic form of analyte loss. It occurs when an element or its compound has a vapor pressure high enough at the temperature encountered during sample preparation to escape from solution into the gas phase. The classic example is mercury: elemental mercury (Hg°) has a vapor pressure of approximately 0.26 Pa at 25°C, meaning that any process that reduces Hg²⁺ to Hg° will result in progressive loss of mercury from an open vessel. Osmium, when oxidized to OsO₄, becomes extremely volatile (boiling point 130°C) and toxic—a concern that Inorganic Ventures addresses directly in our guidance on common problems with Hg, Au, Si, Os, and Na.
Arsenic, selenium, and sulfur can also be lost as volatile hydrides (AsH₃, H₂Se, H₂S), chlorides (AsCl₃ at 130°C, SeCl₄ at 191°C), or oxides under specific digestion conditions. These losses are particularly insidious because they may be partial rather than total, introducing a bias that varies with sample composition and digestion conditions. A study on open-vessel dissolution found that selenium and mercury stability were strongly influenced by the calcium, magnesium, and phosphate content of the sample matrix, with selenium losses occurring when biological samples containing only trace levels of these stabilizing ions were evaporated to complete dryness (Arslan et al., Microchimica Acta).
Adsorption and Surface Losses
Adsorption onto container walls, tubing, and glassware represents a subtler but equally damaging loss mechanism. Mercury is the most notorious offender: Hg²⁺ ions in dilute nitric acid solutions adsorb readily onto plastic surfaces, where they are reduced to elemental mercury at active sites on the container surface. The EPA has documented that low-level mercury in environmental water samples can be lost within days from plastic containers unless stabilization measures are employed (EPA Mercury Preservation Techniques). Inorganic Ventures’ own stability studies have confirmed that mercury at 2–100 ppb is not stable in 1% HNO₃ in LDPE containers, but remains stable in 10% HNO₃ packaged in borosilicate glass (Mercury Chemical Stability).
Gold and silver exhibit similar adsorption behavior in dilute acid matrices. At sub-ppm concentrations, these precious metals can plate onto glass, quartz, and plastic surfaces throughout the sample introduction system, creating persistent memory effects that contaminate subsequent samples. For a comprehensive discussion of how container material and acid matrix interact to affect element stability, see our ICP Operations Guide.
Oxidation-State Instability and Precipitation
Several volatile elements exist in multiple oxidation states, and transitions between states can produce insoluble species that precipitate from solution. Antimony, for example, is stabilized in nitric acid matrices only when complexed with fluoride or tartrate; in the absence of a suitable complexing agent, hydrolysis of Sb(III) can produce insoluble oxides. Tin behaves similarly, requiring fluoride to prevent the formation of metastannic acid (H₂SnO₃) in nitric acid solutions. These redox and hydrolysis reactions are temperature-dependent, pH-sensitive, and matrix-specific—making them difficult to predict from first principles alone.
Inorganic Ventures’ guide on element stability in ICP standards for USP 232 and ICH Q3D provides detailed compatibility data for 24 elements across HNO₃, HCl, and mixed acid matrices, including specific guidance on which complexing ligands are required for problematic elements like Sn, Sb, Os, and Hg.
Element-by-Element Strategies for Preventing Analyte Loss
Mercury (Hg)
Mercury demands more attention during sample preparation than almost any other element. The primary loss pathways are volatilization of Hg°, reduction and adsorption onto plastic container walls, and instability in the presence of certain organic complexing agents (notably tartrate). Effective strategies for mercury preservation include using closed-vessel microwave digestion rather than open hot-block digestion, maintaining solutions in HCl rather than HNO₃ when plastic labware is required, storing dilute mercury solutions in borosilicate glass at concentrations below 100 ppm, and adding gold (Au) as a stabilizing agent at approximately 1 ppm in environmental water matrices.
Inorganic Ventures has conducted extensive in-house stability studies on mercury-containing solutions. Our findings confirm that 0.05–1000 µg/mL Hg solutions are stable in 5% HNO₃ in borosilicate glass for at least one year at room temperature, and that Hg appears to be stable in 10% v/v HCl in LDPE containers. We do not recommend using solutions that contain mercury and antimony tartrate together, as Hg is not stable in these mixtures. For full stability data and practical guidance, see our Mercury Chemical Stability technical paper, and our blog on Mercury Standards for ICP Applications.
Arsenic (As)
Arsenic losses during sample preparation are less common than mercury losses but can be significant under specific conditions. The primary risk is the formation of volatile AsCl₃ (boiling point 130°C) during digestion in hydrochloric acid at elevated temperatures. Open-vessel digestions using aqua regia or HCl-rich mixtures should be performed with care, avoiding prolonged heating above 100°C without a reflux condenser. In most nitric acid digestion protocols, arsenic remains stable because it is oxidized to arsenate (As(V)), which is non-volatile and highly soluble.
When measuring arsenic by ICP-MS, the major analytical challenge is typically spectral interference from ⁴⁰Ar³⁵Cl⁺ on ⁷⁵As⁺ rather than sample preparation losses. Collision/reaction cell technology or mathematical correction equations will address this interference effectively. For sample preparation guidance specific to arsenic, including digestion protocols and matrix compatibility, visit the Arsenic Sample Preparation Guide in our technical library.
Selenium (Se)
Selenium is one of the more treacherous volatile elements because losses can be both large and inconsistent. Selenium can be lost as volatile SeCl₄ during digestion in HCl or aqua regia, as H₂Se in strongly reducing environments, or as elemental selenium through reduction to Se°, which precipitates as a red amorphous solid. The risk of volatilization is greatest during open-vessel digestion when samples are heated to dryness—a step that should be strictly avoided whenever selenium is an analyte of interest. Research has demonstrated that the stability of selenium during open-vessel evaporation depends on the sample’s mineral content, with calcium and magnesium acting as stabilizing agents that reduce selenium volatility (Arslan et al., Microchimica Acta).
For ICP-OES analysis, selenium’s primary emission lines in the vacuum ultraviolet (196.026 nm, 203.985 nm) are inherently noisy and require optimized plasma conditions for acceptable precision. Laboratories experiencing poor %RSD for selenium should review both their sample preparation protocol (to confirm quantitative recovery) and their instrument configuration (to ensure sufficient plasma energy at these low UV wavelengths). See this post from Inorganic Ventures’ Ask the Experts forum that addresses these issues in detail.
Boron (B)
Boron’s volatility arises from its tendency to form boric acid (H₃BO₃) and subsequently trimethyl borate or metaboric acid upon heating. In open-vessel digestions, boron can be lost as volatile B(OH)₃ at temperatures exceeding 100°C, particularly in the absence of a complexing agent. An equally important concern is contamination: boron is readily leached from borosilicate glassware, making it one of the most common sources of blank contamination in ICP laboratories that use glass sample introduction systems or glass volumetric ware.
Inorganic Ventures’ Boron Sample Preparation Guide documents that boron at 2–100 ppb is stable for months in 1% HNO₃, while solutions at 1–1000 ppm are stable for years. Higher concentrations (1000–10,000 ppm) benefit from stabilization with dilute ammonium hydroxide. For boron analysis, avoiding glass containers and HF-containing solutions (which compete for boron complexation) is essential. Boron is one of the elements targeted by our ICP-TRUE-RINSE washout solution, which was specifically developed to address memory effects from sticky elements like Hg, Au, B, and Os.
Sulfur (S) and Iodine (I)
Sulfur and iodine share the challenge of forming volatile species under acidic, heated conditions. Sulfur can be lost as SO₂ during aggressive oxidizing digestions, while iodine readily forms volatile HI, I₂, and ICl under a range of acid conditions. Iodine is particularly difficult to retain during open-vessel nitric acid digestions because oxidation to iodate followed by disproportionation can release elemental iodine vapor even at moderate temperatures.
For sulfur, maintaining an oxidizing environment throughout digestion ensures conversion to stable sulfate (SO₄²⁻), which is non-volatile and highly soluble. For iodine, the use of alkaline extraction or stabilization with a mild reducing agent (e.g., ascorbic acid) can prevent oxidative loss. Closed-vessel microwave digestion is particularly beneficial for both elements, as the sealed environment prevents gas-phase losses entirely. Inorganic Ventures’ Sample Preparation Guides provide element-specific protocols for sulfur and dozens of other elements, with detailed information on acid compatibility, digestion temperature, and storage conditions.
Osmium (Os), Antimony (Sb), and Tin (Sn)
Osmium occupies a unique position among volatile elements because its volatile oxide (OsO₄) is both extremely toxic and readily formed in the presence of any oxidizing agent, including dilute nitric acid. Inorganic Ventures explicitly advises that osmium should never be exposed to oxidizing agents, and that all work with Os should be conducted exclusively in HCl-containing solutions using glass introduction systems where possible (Common Problems with Os).
Antimony and tin require complexing ligands—fluoride being the most effective—to remain stable in nitric acid solutions. Without fluoride, antimony undergoes hydrolysis at moderate acid concentrations and precipitates as oxides, while tin forms insoluble metastannic acid. For applications requiring Sb and Hg together, note that tartrate-stabilized antimony is incompatible with mercury: Hg is not stable in the presence of tartrate. A HNO₃-HF matrix is recommended when simultaneous analysis of Sn, Sb, and Hg is required (USP 232 Element Stability Guide).
Digestion Strategies: Open Vessel vs. Closed Vessel
The choice between open-vessel and closed-vessel digestion has a direct and often decisive impact on volatile element recovery. Open-vessel digestion—whether on a hot plate, in a graphite hot block, or under reflux—operates at or near the boiling point of the acid mixture, typically 100–130°C for nitric acid. At these temperatures, volatile species of Hg, As, Se, S, I, and Os can escape into the atmosphere, even with reflux condensers in place. This limits open-vessel methods primarily to matrices where volatile elements are not target analytes, or where the sample matrix inherently stabilizes the analytes (e.g., high calcium matrices stabilizing selenium).
Closed-vessel microwave digestion eliminates volatile losses by sealing the reaction vessel before heating, allowing temperatures to exceed 200°C and pressures to reach 40–200 bar depending on the system. Because no gas-phase escape is possible, volatile species that form transiently during digestion are retained in solution and re-dissolved as the vessel cools. This makes microwave digestion the method of choice for multi-element protocols that include mercury, selenium, arsenic, and other volatile or semi-volatile analytes. The dramatically higher temperatures achievable in closed vessels also improve digestion efficiency and reduce residual carbon, which can cause signal suppression and spectral interferences in ICP-MS.
For a comprehensive overview of acid digestion chemistry, including the properties of nitric, hydrochloric, sulfuric, hydrofluoric, and perchloric acids and their applications in sample preparation, see the Inorganic Ventures article on Understanding the Chemistry of Acid Digestion.
Matrix Selection, Container Compatibility, and Storage
Choosing the Right Acid Matrix
The acid matrix in which samples and standards are prepared and stored is one of the most consequential decisions in any analytical workflow involving volatile elements. Nitric acid (HNO₃) is the default matrix for most ICP applications because it is a strong oxidizer with minimal spectral interferences. However, it is incompatible with osmium (forms OsO₄), and presents stability challenges for mercury (adsorption from dilute solutions in plastic), tin & antimony (hydrolysis without fluoride).
Hydrochloric acid (HCl) resolves many stability issues—it is the preferred matrix for mercury, gold, and the platinum group metals—but introduces chloride-based polyatomic interferences in ICP-MS (⁴⁰Ar³⁵Cl⁺ on ⁷⁵As, ³⁵Cl¹⁶O⁺ on ⁵¹V, etc.) that must be managed through collision/reaction cell technology or alternative mass selection. Inorganic Ventures’ detailed guide on acid matrix selection for ICP elemental compatibility provides a comprehensive element-by-element reference for selecting the optimal acid system for your analyte list.
Container Material Selection
Container material interacts directly with acid matrix and analyte concentration to determine solution stability. The key decision for volatile elements is between polyethylene (LDPE/HDPE), polypropylene, borosilicate glass, and fluoropolymers (PTFE, PFA, FEP). Mercury at sub-ppm concentrations requires borosilicate glass when stored in HNO₃, but is stable in HCl in plastics. Boron must never be stored in borosilicate glass due to leaching contamination. Appropriate concentrations of silver in HCl solutions require protection from light regardless of container material.
The Inorganic Ventures ICP Operations Guide includes detailed element-by-element compatibility charts showing which combinations of acid matrix and container material are acceptable, along with practical notes on photosensitivity, temperature storage requirements, and the role of stabilizing agents like gold (for mercury) and fluoride (for tin and antimony).
Temperature and Time Considerations
Temperature management is critical at every stage of the workflow. During digestion, excessive temperature in open vessels drives volatile species into the gas phase. During storage, elevated temperatures accelerate adsorption reactions and redox transformations. Even during analysis, the time a sample sits in an autosampler tray at room temperature can matter for highly unstable species like mercury at very low concentrations.
Best practice for volatile elements is to prepare standards fresh from concentrated stock solutions on the day of analysis, keep digested samples capped and refrigerated (4°C) until measurement, and minimize the time between final dilution and aspiration into the ICP. For laboratories with high sample throughput, scheduling volatile-element-containing batches early in the analytical run reduces the accumulated time that working standards sit on the autosampler.
Calibration, Quality Control, and Recovery Validation
Matrix-Matched Standards for Volatile Elements
Accurate calibration for volatile elements requires not only concentration matching, but matrix matching. A mercury standard prepared in HCl will have different nebulization, transport, and ionization characteristics in the plasma compared to a mercury solution in HNO₃. If the samples were digested in aqua regia and the standards are in 2% HNO₃, the mismatch in acid composition, total dissolved solids, and viscosity will introduce bias that internal standardization may only partially correct.
Inorganic Ventures manufactures single-element and multi-element ICP and ICP-MS standards in a range of acid matrices, including HNO₃, HCl, HNO₃/HCl, HNO₃/HF, and specialty matrices. For laboratories with complex or unusual sample compositions, our custom standards service can produce multi-element blends in any compatible matrix at any required concentration, formulated by our experienced chemists to ensure long-term stability and element compatibility.
Spike Recovery and Method Validation
Spike recovery studies are essential for validating that the complete sample preparation and analysis workflow preserves volatile analytes. The spike must be added to the sample before digestion, not after, to test the entire preparation path. Acceptable recovery for most regulatory methods is 80–120%, though tighter criteria (85–115%) may apply for specific applications. If spike recoveries consistently fall below acceptable limits for a volatile element, the first diagnostic step is to identify where in the preparation workflow the loss occurs—during digestion, during transfer and dilution, or during storage.
Using a CRM that has been independently certified for the volatile element of interest provides additional validation. If the CRM recovery agrees with the certified value but the spike recovery does not, the problem is likely in the spike preparation or addition step. If both the CRM and the spike fail, the digestion or storage protocol is the more likely source of the loss. Inorganic Ventures’ certified reference materials are manufactured with certified values traceable to NIST SRMs through two independent methods, providing the highest level of confidence for method validation.
Managing Memory Effects and Carryover
Volatile and adsorption-prone elements create persistent memory effects in ICP sample introduction systems. Mercury, gold, boron, osmium, and silicon are the most common culprits, and inadequate washout between samples can contaminate low-level measurements with carryover from previous high-concentration samples. Traditional rinse protocols using dilute HNO₃ or HCl are often insufficient for these elements.
Inorganic Ventures developed ICP-TRUE-RINSE, a purpose-built washout solution specifically formulated to address memory effects from the most problematic elements. Testing has demonstrated that ICP-TRUE-RINSE significantly reduces wash volume and wash time compared to conventional acid rinses. Laboratories analyzing volatile elements at trace levels should consider replacing their standard rinse protocols with a dedicated washout solution to improve both throughput and data quality.
Building a Robust Workflow: Practical Recommendations
Bringing together the principles discussed in this article, a robust sample preparation workflow for volatile elements should incorporate the following practices. First, use closed-vessel microwave digestion whenever mercury, selenium, arsenic, or iodine are target analytes. The sealed environment eliminates gas-phase losses and permits higher digestion temperatures for improved recovery. Second, select the acid matrix based on your complete analyte list, considering both stability requirements and potential ICP-MS spectral interferences. Consult our acid matrix selection guide for element-specific recommendations.
Third, match your container material to your matrix and analyte concentration. Use borosilicate glass for low-level mercury in HNO₃, leached LDPE for mercury in HCl, and avoid borosilicate glass entirely for boron analysis. Fourth, prepare working standards from concentrated stock solutions on the day of analysis for the most volatile analytes, and store all digested samples capped and refrigerated until measurement. Fifth, validate your complete workflow with spike recoveries performed before digestion and with independently certified CRMs from a manufacturer like Inorganic Ventures whose standards are ISO 17034 and ISO 17025 accredited with full traceability documentation.
Finally, implement a dedicated washout protocol using a purpose-formulated rinse solution rather than a generic acid rinse. Memory effects from mercury, gold, boron, and osmium are among the most persistent sources of carryover error in trace-level ICP analysis, and addressing them proactively prevents contamination before it occurs.
Purchase properly engineered CRMs with Inorganic Ventures
Volatile and semi-volatile elements do not forgive careless sample preparation. The mechanisms of loss—volatilization, adsorption, oxidation-state instability, and precipitation—are well understood, and in nearly every case, the loss can be prevented through deliberate choices in digestion chemistry, vessel selection, acid matrix, and storage conditions. The key is to treat each of these difficult elements with the specific attention it requires, rather than assuming that a one-size-fits-all preparation protocol will deliver quantitative recoveries.
Inorganic Ventures’ extensive library of sample preparation guides, stability studies, and technical resources provides the detailed, element-specific guidance that laboratories need to build robust methods for even the most challenging analytes. When paired with properly engineered CRMs manufactured in the correct matrix and stored under validated conditions, these practices ensure that the number reported by the instrument accurately reflects the concentration of the element in the original sample—which is, after all, the entire point.
To discuss your specific volatile element challenges, contact our technical team for a free consultation. Browse our complete range of single-element standards, explore the product catalog, or submit a Custom Quote Request for a tailored formulation matched to your exact needs.
References and Further Reading
External Sources:
1. Arslan, Z. et al. (2009). Assessment of matrix-dependent analyte stability and volatility during open-vessel sample dissolution for As, Cd, Hg, and Se – Microchimica Acta (Springer)
2. EPA Mercury Preservation Techniques – Inorganic Ventures hosted PDF
3. Chemical Vapor Generation AFS for As, Sb, Se, and Hg in Geological Samples – Spectroscopy Online
Inorganic Ventures Resources:
• Chemical Stability and Compatibility
• Mercury Standards for ICP Applications
• Common Problems with Hg, Au, Si, Os, and Na
• USP 232 / ICH Q3D Element Stability Guide
• Acid Matrix Selection for ICP
• Understanding the Chemistry of Acid Digestion
• ICP-TRUE-RINSE Washout Solution
• Certified Reference Materials
• Chemistry Resources / Technical Library