Sample preparation by microwave assisted closed vessel digestion

Sample preparation by microwave assisted closed vessel digestion for determination of elemental impurities based on USP chapter 232 and 233




After long decades relying on old-fashion comparative visual measurements based on formation of metal ions precipitate with sulfide, all strategies for determination of metals in pharmaceuticals are changing based on new USP 232 (Elemental Impurities – Limits) and USP 233 (Elemental Impurities – Procedures) protocols. Nowadays, there are efforts towards harmonization of legislation among USP, European Community, Japan and other pharmacopeias and it seems clear that metals determination will strongly rely on microwave-assisted closed vessel digestions and determinations using ICP-based techniques, i.e., ICP OES and ICP-MS. This is clearly affecting the pattern of papers published in the area and they are moving from specific applications considering type of samples and analytes to general procedures with analytical capability for determining many analytes in several types of samples. Efforts in this direction are underway and there is plenty of room for the development of microwave-assisted digestion procedures. The development of these procedures will be critically dependent on the choice of the acid digestion mixture and the use of closed vessels to support high pressures and, consequently, allowing operation at high temperatures.

Materials & Methods

In our everyday lives, people are exposed to a variety of chemical substances, some of which may be harmful to their health at relatively low exposure concentrations. The use of toxic substances may be banned or restricted by national or international authorities, according to the outcome of substance- and exposure-specific risk assessment. ‘‘Heavy metals’’ have been the subject of elaborate toxicological research, which has led to subsequent efforts to limit human exposure to several toxic metals. Such efforts include the formulation of guidelines stating limit concentrations in consumer products, food and beverages, drinking water and environmental compartments.


Recently, USP has published proposals for new general chapters concerning limit concentrations of various elemental impurities and proposed new analytical procedures to accurately determine them at the suggested limit concentrations. The respective documents,4,5 which are currently in the process of revision, are Chapters 232, Elemental Impurities – Limits, and 233, Elemental Impurities – Procedures. For Chapter 232, target elements were selected on the basis of toxicity and limit concentrations were calculated based on permitted daily exposure for a person with a body weight of 50 kgs.


Depending on the analytical procedure adopted and sample analyzed, acid types and concentrations used were either 1% (v/v) HNO3, 10% (v/v) HNO3 or one of following mixtures of HCl and HNO3: 6% (v/v) of a 5 : 1 HCl : HNO3 mixture, 2% (v/v) of a 1 : 1 HCl : HNO3 mixture, 10% (v/v) of a 3 : 1 HCl : HNO3 mixture or 10% (v/v) of a 1 : 3 HCl : HNO3 mixture. As indicated, microwave-assisted acid digestion was performed to aid in sample dissolution, using a Milestone Ethos UP System.

Quality Analysis with great sample preparation

The new ETHOS UP is simply the most advanced yet easy to use system for microwave sample preparation we have ever manufactured. It offers a perfect integration between microwave hardware, user interface, digestion sensors and pressure vessels.


The ETHOS UP fully embodies Milestone’s philosophy in microwave sample preparation. Specifically designed for closed vessel microwave acid digestion, it offers productivity, safety, ease of use, connectivity, expertise and application flexibility.
Featuring a comprehensive choice of accessories, ETHOS UP microwave digestion system encompasses Milestone’s visionary concept of “Total Microwave Sample Preparation” offering a complete first-class solution for microwave solvent extraction, high-temperature fusion, vacuum evaporation and even organic and inorganic synthesis or protein hydrolysis.

  • Safety and reliability.Best microwave hardware, temperature and pressure sensors
  • Performance and throughput.easyTEMP temperature control and advanced rotor technology
  • Ease of use and control.EasyCONTROL operating software
  • Expertise and know-how.30-years experience at your lab with the Milestone Connect
  • Rotor-based digestion system for hundreds of applications.


The ETHOS UP fully embodies Milestone’s philosophy towards, and knowledge of, microwave sample preparation. Specifically designed for closed vessel acid digestion, it offers a perfect integration of microwave hardware, user interface, reaction sensor technology and pressure resistant vessels. The ETHOS UP is the most powerful system in the market, with two magnetrons and a total power of 1900 Watts. Microwave homogeneity is assured through a dedicated microwave diffuser. Safety and reliability are Milestone’s priorities. Both factors are ever present in the foundation of the ETHOS UP’s design. The cavity has a volume in excess of 70L, and is constructed entirely of stainless steel to ensure longevity and structural integrity. Our unique pressure responsive door, also made of stainless steel, ensures superior safety even with the most reactive samples. The safeVIEW high definition digital camera, allows to safely look into the microwave cavity.


Regardless of the samples you’re trying to digest, the Milestone SK-15 rotor is always an effective option to simplify your journey from sample to analysis, even with hard-to-digest samples. The SK-15 is a high- pressure and high-temperature rotor with a capacity of up to 15 PTFE vessels of 100 mL suitable for digestion of polymers, large food and feed samples, pharmaceuticals, alloys and geological materials. The table shows the recovery study with the SK-15 on pharmaceutical samples. The simplified design of the rotor coupled with its large vessel capacity ensures high productivity without compromising on performance. Safety is assured by our unique vent- and-reseal technology, the foundation of Milestone’s position as the leader in closed vessel microwave digestion. Milestone has recently evolved this already advanced technology (US Patent 5,270,010), providing the operator with unsurpassed safety and performance capabilities by further increasing the temperature and pressure capacities of the vessels. A safety spring built into the cover allows for precise venting of the vessel, if that should occur. Once the pressure has been reduced to a containable level, the cover closes again. Only the excess pressure, mainly generated by CO, NO, fumes, is therefore released, allowing for a complete recovery of even volatile elements.


The microwave cavity has a volume of over 70 liters, the largest currently available. Therefore, digestion rotors with more sample places can be accommodated, incresing both productivity and sample throughput. Secondly, it improves the inherently safety because a larger cavity contains gases escaping from vessels in a more efficient way, in case of a sudden over pressurization.


For additional safety, the ETHOS UP features a full stainless steel door with an innovative opening and self-resealing mechanism. Should there be a sudden over pressurization of the cavity, the door slightly opens for rapid and safe pressure release and the microwave power is instantaneously cut off. Immediately afterwards, the door is pulled back, resealing the microwave cavity.


The ETHOS UP is equipped with two 950 Watt magnetrons for a total of 1900 Watt. The system additionally employs a rotating diffuser that evenly distributes the microwaves throughout the cavity. High power coupled with this diffuser enable very fast heating of high throughput rotors and the complete digestion of the most difficult samples.


The ETHOS UP integrates the Milestone safeVIEW, a high definition digital camera interfaced with the instrument terminal. It allows the chemist to monitor the progress of the digestion whilst being fully protected by the instrument’s all-stainless steel door. A video of the entire run is shown in real time.

to save your time


  • Hundreds of methods factory stored
  • Visual indication of temperature and pressure values
  • Methods and runs printed or saved as PDF files
  • Instrument’s trail tracking (CFR-21 Part 11 compliance)
  • Easy-to-read, bright, full-color, touchscreen display
  • Icon-driven, multi-language software

Temperature control with easyTEMP

The easyTEMP contactless sensor directly controls the temperature of all samples and solutions, providing accurate temperature feedback to ensure complete digestion in all vessels with superior safety. This technology combines the fast and accurate reading of an in-situ temperature sensor with the flexibility of an infrared sensor.
The ETHOS UP software provides digestion history traceability and temperature measurement for every sample. Temperature diagrams and profiles are displayed in real-time, and can be saved on the ETHOS UP terminal.


Milestone Connect is a unique feature for your best-in-class system putting Milestone 30-years of applications experience at your fingertips.
By choosing ETHOS UP, ETHOS EASY, ETHOS LEAN, ultraWAVE or DMA-80 evo, you will get exclusive access to the knowledge and experience of the Milestone scientific community and application team: continuously updated application notes, library of scientific papers, video tutorials, system manuals are available at any time – 24/7. The Milestone Connect can remotely monitor the operation of your microwave digestion system or direct mercury analyzer through your desktop, tablet or smartphone device, thus enhancing your enhancing your sample preparation or analysis procedure.



Unique customer resource center

Solid experience combined with perfect technologies to remotely monitor functionality of equipment helped our application team to develop Milestone Connect. Milestone 30-years of experience are perfectly realized in Connect product – ideal solution for forward-looking laboratories willing to have more knowledge and use cutting-edge instruments.
By logging-in, they will be able to be part of Milestone scientific community and tap into unlimited resources. Milestone know-how and 30-year experience in sample preparation are now available for chemists to provide with instant support available 24 hours a day, 7 days a week.

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