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Ph. Eur. 2.2.48 Raman Spectroscopy: How Raman instruments from Metrohm comply with the 2022 update

Ph. Eur. 2.2.48 Raman Spectroscopy: How Raman instruments from Metrohm comply with the 2022 update

by | Nov 29, 2021 | Analysis, Company

The European Pharmacopoeia (Ph. Eur.) is a single reference work for the quality control of medicines. Ph. Eur. contains norms, suggests analytical methods, and lists many properties that define quality control (QC) during the production of medicines, the raw materials used, and the instruments required to perform such tests. These official standards are legally binding in several countries – not only in Europe, but worldwide.

Raman spectrometers—especially handheld and portable instruments—are increasingly used for QC of medicines and raw materials (RMID). Instrument interfaces are user-friendly, requiring little technical expertise, and they provide flexible sampling options for most sample types with rapid, non-destructive measurements.

Metrohm’s Raman systems exhibit great flexibility—from see-through to standoff to immersion sampling.
An excerpt from the Ph. Eur. 2.2.48 Raman Spectroscopy chapter says:
«Raman spectroscopy is commonly used for qualitative and quantitative applications and can be applied to solid, liquid, and gaseous samples. Raman spectroscopy is a rapid and non-invasive analytical method and can be performed off-line, at-line, on-line, or in-line[…] Raman spectrometers can be situated far from the point of measurement using long-distance optical fibres to collect the Raman signal.»

For a look at RMID from start to finish, download our free four-part tutorial series.
Handheld Raman for RMID in pharma and other regulated industries
Technological developments and their increasing adoption in the pharmaceutical industry prompted a revision of Ph. Eur. 2.2.48 which ensures the reliability of Raman results. The updated chapter 2.2.48 was published in the Ph. Eur. Supplement 10.7 (October 2021) and will ultimately take effect in April 2022.

While much of the Ph. Eur. 2.2.48 chapter has remained the same, the latest revision features:

  • new requirements for spectral resolution for qualitative Raman analysis using a suitable reference material
  • updated requirements for the Raman response-intensity scale
  • detailed procedures for the comparison of spectra

We will address these new requirements across our Raman spectroscopy product lines in the rest of this article.

Spectral Resolution

«Spectral resolution is the ability of a spectroscopic system to separate adjacent bands, which makes it possible to characterise complex samples (e.g., brand analysis, crystallinity, polymorphism).

[…] For identity tests, unless otherwise prescribed in a monograph, the spectral resolution must be less than or equal to 15cm-1 (measured in the wavenumber range between 1000cm-1 and 1100cm-1).

The spectral resolution is verified using a suitable reference material. The instrument parameters used for the test, such as laser, slit-width and grating for dispersive instruments and circular aperture […] for FT-instruments, must be the same as those applied for sample measurements. For example record the Raman spectrum of calcium carbonate for equipment qualification CRS, and determine the full width at half height (W1085) of the band located at 1085 cm-1. The spectral resolution (R) using calcium carbonate is then given by the following relation:»

Handheld Raman instruments: MIRA P and NanoRam

All MIRA P and NanoRam devices (including both NanoRam and NanoRam-1064) for the pharmaceutical industry are designed and tested to meet stringent resolution requirements. During QC, the resolution of each instrument is tested to be less than 15 cm-1 against a secondary USP (US Pharmacopeia) reference standard of calcium carbonate according to ASTM E2529, which is the same procedure recommended in this newly released Ph. Eur. chapter.

The measured spectral resolution value for each instrument, along with its identifying serial number, is included in the instrument final test report. A certificate or final test report is packaged with the device and sent to the customer (starting in April 2022 for MIRA P). This resolution is fixed by the optical design of the instrument and is stable over time.

Portable Raman instruments: i-Raman series, QTRam, STRam, and PTRam

The instrument resolution for all of Metrohm’s portable Raman instruments from B&W Tek are factory-tested with calcium carbonate and displayed on final instrument test reports. The spectral resolution is dependent on the instrument design and defined for each specific instrument configuration. Depending on the instrument model, the spectral resolution is between 3.5–11 cm-1. Additionally, the instrument control softwares Vision and BWAnalyst have the performance test function that verifies spectral resolution using the 1001.4 cm-1 peak of polystyrene.

Handheld and portable Raman instruments from B&W Tek.

Response-Intensity Scale

«The verification of the response-intensity scale is principally performed for quantitative methods.

Appropriate acceptance criteria will vary with the application. A maximum variation of ± 10 per cent in band intensities compared to the previous instrument qualification is achievable in most cases. Response calibration may involve the use of white-light standards or luminescent glass (e.g., NIST SRM 2241).»

Handheld Raman instruments: MIRA P, MIRA M-3, and NanoRam series

MIRA P, MIRA M-3, and NanoRam systems are designed for qualitative analysis, not for quantitative purposes. Therefore, this criterion is not a strict requirement for handheld Raman products.

However, the relative intensity response of MIRA P and NanoRam series instruments is calibrated with a NIST standard SRM calibration material (SRM 2241, SRM 2242) or NIST SRM 2241-traceable calibration standard to achieve better uniformity from instrument-to-instrument.

The NanoRam series instruments have an acceptance criterion for relative intensity response in the instrument performance validation in alignment with Ph. Eur. 2.2.48 and USP<858>. To pass the performance validation, <10% relative intensity error is required using the factory-supplied polystyrene cap.

Portable Raman instruments: i-Raman series, QTRam, STRam, and PTRam

The relative intensity response of these portable Raman instruments is calibrated using a proper NIST standard SRM calibration material to achieve better uniformity from instrument-to-instrument. Additionally, the Vision instrument control software includes the performance test function that verifies the intensities of several Raman peaks of polystyrene relative to its 1001.4 cm-1 peak, to a maximum variation of ±10% compared to the previous instrument qualification.

Comparison Procedures

For qualitative methods, additional information for identification has been defined.

«Several comparison procedures may be used, and the analyst must document and justify the method used and the specific acceptance criteria that allow a conclusion for identification. The spectra can be compared by either overlaying the spectra (in the whole spectral range or in the region of interest specified in the monograph) or by using mathematical calculations of the software. It is possible for example to perform:

  • visual comparison based on band positions and relative intensities unless otherwise specified[…]
  • a statistical determination of the similarity between the spectra of the material to be examined and the reference standard[…]
  • evaluation by chemometric methods[…]»

While an experienced Raman spectroscopist can certainly compare spectra visually and assess sample validity based on peak location, fluorescence, saturation, and signal-to-noise ratio, the widespread implementation of Raman in the real world means that complex analysis must be done by the device and not the user. Statistical comparison methods are used primarily for identification of unknowns through correlation of a sample spectrum with library spectra. The software performs library searches and returns a Hit Quality Index (HQI) value indicating the level of correlation as defined by a user-defined threshold.

Chemometric methods rely on dimensionality-reduction methods that are performed by the software, such as Principal Component Analysis (PCA), where new sample data is compared within a multivariate model created from representative samples. This permits highly accurate verification of known materials according to how well a spectrum fits into the model limits, which are determined by a confidence interval. In the analysis of medicines and raw materials, chemometric methods are used to distinguish the quality and consistency of a material. MIRA P (and its dedicated software, MIRA Cal P) and NanoRam instruments use both statistical and chemometric methods for sample identification and verification based on the needs of the end-user.

For more information, download our free technical and application notes as well as a White Paper below.

Pros and Cons of Using Correlation vs. Multivariate Algorithms for Material Identification via Handheld Spectroscopy
Method Development with NanoRam®-1064
Simplified RMID Model Building – Mira Cal P and Model Expert
White Paper: Verification, p-values, and Training Sets for the Mira P

Wavenumber accuracy requirements of Ph. Eur. 2.2.48

«Verify the wavenumber scale for Raman shifts using a suitable standard that has characteristic maxima at the wavenumbers under investigation, for example an organic substance such as polystyrene, paracetamol or cyclohexane[..]

A minimum of 3 wavenumbers covering the working range of the instrument intended for measurements should be selected.[…]»

This chapter maintains the same requirements for Raman wavenumber accuracy and is consistent with the USP <858> and JP 2.26. All of Metrohm’s handheld Raman instruments meet these requirements. Users are recommended to run performance validation tests at regular intervals using polystyrene or another ASTM Raman shift calibration material.

Download our free White Paper below to learn more about instrument calibration, system verification, and performance validation.

Instrument Calibration, System Verification, and Performance Validation for Metrohm Instant Raman Analyzers (Mira)
The Calibrate/Verify Attachment (CVA) shown here is a dual-ended accessory containing a toluene/acetonitrile ASTM standard for calibration/verification of the wavenumber axis and polystyrene for a second wavenumber verification according to Ph. Eur. 2.2.48.
Performance tests for Raman wavenumber accuracy are included the Vision and BWAnalyst softwares for the i-Raman series and other portable Raman products (STRam, QTRam, PTRam), with acceptance criteria in accordance with the pharmacopeial requirements.

Metrohm’s unique way of compliance with Ph. Eur. 2.2.48

Better representation of the material

«When using Raman spectroscopy[…] care must be taken to ensure that the measurement is representative. This can be achieved by, for example rotation of the sample, performing multiple measurements on different preparations of the sample, using orbital raster scanning (ORS), increasing the area of illumination by reducing the magnification, by demagnification of the laser beam or by changing the focal length between measurements to scan at different depths.»

ORS™ is Metrohm Raman’s proprietary method for moving the excitation laser in a pattern over a sample in order to collect more representative data from a larger area of the sample, especially on heterogeneous samples. All MIRA and MISA instruments are equipped with ORS.
Learn more about ORS by downloading the related Application Note.
Improving verification with Orbital Raster Scan technology
For more details about how we comply, please check the U.S. Pharmacopeia Raman Chapters Updates page on the B&W Tek website. For more general information, download this General Compliance Statement for MIRA handheld Raman systems
B&W Tek: U.S. Pharmacopeia Raman Chapters Updates
MIRA General Compliance Statement
For a more comprehensive look at raw material identification and verification in the pharmaceutical industry, there is a significant amount of information on this topic in our related blog post.
Real World Raman: Simplifying Incoming Raw Material Inspection

Post written by Dr. Melissa Gelwicks (Technical Writer at Metrohm Raman, Laramie, Wyoming), and Dr. Xiangyu (Max) Ma (Handheld Raman Product Manager) and Dr. Jun Zhao (R&D Director) at B&W Tek, Plainsboro, New Jersey.

The evolution of handheld 785 nm Raman spectroscopy: Raman extraction from fluorescence interference

The evolution of handheld 785 nm Raman spectroscopy: Raman extraction from fluorescence interference

by | Nov 1, 2021 | Analysis, Company, Fundamentals

MIRA DS (Metrohm Instant Raman Analyzer) is a handheld Raman system that identifies materials using 785 nm laser excitation. The advantages of using 785 nm Raman are well understood. Excitation with shorter wavelengths produces strong Raman scattering with short acquisition times. This results in a high signal-to-noise ratio and provides excellent spectral resolution with lower power draw. These are just some of the reasons that handheld Raman has become so popular over the last two decades.

The sensitivity of Raman at 785 nm also means that lower laser powers can be used. Lower laser powers help to protect sensitive samples from burning or ignition. The silicon detectors used at shorter wavelengths do not need to be cooled, further extending battery lifetimes. The net result is that 785 nm systems can be very small and still provide fast and accurate material identification for long hours in the field.

Learn more about how MIRA became mobile in our previous blog post.
«Analyze This»: How Mira Became Mobile
However, while this is considered the «sweet spot» for both a strong signal and fluorescence mitigation among possible wavelengths, approximately 10% of Raman active materials fluoresce under interrogation with 785 nm Raman systems [1]. For example, Gum Arabic is a widely used filler and binding agent. When sampled with 785 nm systems, its fluorescence overwhelms the Raman signal (more on this subject later). Similarly, cutting agents (e.g., sucrose found in street drugs) fluoresce and can prevent positive identification of the target substance. Dyes can be problematic in the analysis of tablets, foodstuffs, art, and plastics as well. Often, weak Raman features can still be observed in fluorescent materials with 785 nm interrogation, but fluorescence mitigation is crucial for library matching.

Previous recommendations to overcome fluorescence

When fluorescence is an issue, 1064 nm laser excitation is often recommended. The tradeoffs include higher laser power, increased sample heating, longer interrogation times, and low Raman scattering efficiency. Often, this means larger instruments with shorter battery lifetimes. Instruments from some manufacturers require longer acquisition times that slow down sampling and can potentially damage the sample.

Is there a better way?

In a word, yes. SSE (Sequentially Shifted Excitation) can be used to remove fluorescent contributions to a Raman spectrum by using a laser that shifts the excitation wavelength as a function of the laser temperature. The result is a very large «handheld» system with a shoulder strap and a high price tag, partly due to the expensive laser used. Aside from the bulk and the cost, another issue with these systems is that the constant temperature cycling of the laser causes the system’s battery to have a short lifetime.

A Metrohm solution

Metrohm Raman has designed a fluorescence rejection system based on its compact MIRA DS package using an IPS single-mode 785 nm laser. The system is capable of producing excellent spectral resolution and flat baseline data with low laser power, short acquisition times, and all of the other excellent functionalities that users have come to expect from MIRA DS.

This fluorescence rejection system is built upon a MIRA DS platform, preserving all of its unique capabilities:

Safety in Any Situation – Addressing the needs of first responders
Improving verification with Orbital Raster Scan (ORS) technology
Mira DS and KnowItAll Raman Spectral Library (Handheld) from Wiley
Smart Acquire – Automated Raman Material ID for Defense and Security Professionals
On-site Identification of Improvised Incendiary Devices: Integrated Chemical ID and Decision Guidance with MIRA DS and HazMasterG3®
Determination of Heroin in Street Drug Samples

MIRA XTR DS

MIRA XTR DS is the evolution of Raman spectroscopy. It combines the smaller size, higher resolution, and lower power consumption of a 785 nm Raman instrument with patent-pending advanced algorithms to eXTRact Raman data, even from spectra that have strong fluorescence!
Figure 1. Comparison of Raman spectra of Gum Arabic powder measured by 1064 nm, 785 nm (MIRA DS), and XTR® (MIRA XTR DS).
Figure 1 contains Raman spectra from a fluorescent material, Gum Arabic powder, with traditional 785 nm and 1064 nm laser excitation, in addition to MIRA XTR DS. The improvement in resolution with XTR is obvious. Notice the very flat (uncorrected) baseline in the XTR spectrum on the bottom. This is crucial for library matching with a Pearson correlation, where the dot product between spectra and non-zero baselines contribute strongly to the correlation.

Learn more about MIRA XTR DS on our website.

MIRA XTR DS: The evolution of handheld Raman for fluorescence-free material identification
Applications for MIRA XTR DS include Sensitive Site Exploitation / Intelligence Surveillance Reconnaissance (SSE/ISR) of clandestine labs and determination of synthetic routes to illicit products. MIRA XTR DS is designed for real world scenarios like the analysis of methamphetamine lab residues and identification of narcotics in street drug samples. This includes ID of narcotics, despite cutting agents that fluoresce and fail analysis at 785 nm. ORS™ combined with fluorescence rejection means that MIRA XTR DS can also delicately interrogate sensitive materials like colored explosive compounds.

Download our free White Paper below to find out more about the capabilities of MIRA XTR DS.

White Paper: Fluorescence-free 785 nm material identification with MIRA XTR DS

Classic applications improved with MIRA XTR DS

Lidocaine [2] is a local anesthetic that can also be used to cut cocaine because it enhances the immediate numbing sensation that many cocaine users associate with a high quality product. Since cocaine is typically present at only ~30% in street samples, its signal can be occluded by other components in the mixture. However, positive identification of common cutting agents like lidocaine can lead to further investigation of a suspect sample.

Traditionally, lidocaine was an issue for 785 nm Raman systems, as its fluorescence prevented both positive identification of lidocaine and detection of cocaine. MIRA XTR DS produces an excellent, fluorescence-free, resolved spectrum of lidocaine (Figure 2).

Figure 2. Comparison of Raman spectra of lidocaine hydrochloride measured by 1064 nm, 785 nm (MIRA DS), and XTR (MIRA XTR DS).
Diphenhydramine is another example of a common OTC drug that, when detected, may suggest darker dealings. It can be abused on its own, but it is also a potential precursor in the synthesis of methamphetamine. Diphenhydramine exhibits some fluorescence when interrogated with 785 nm Raman (Figure 3), but it is also typically present in mixtures with inert ingredients that fluoresce. For this type of analysis, SERS can be used to detect trace amounts of a substance. This is an excellent showcase for MIRA XTR DS, because it can perform both 785 nm Raman and SERS tests, while most 1064 nm systems currently on the market cannot be used for SERS analysis.
Figure 3. Left: MIRA XTR DS used for no-contact testing. Right: Comparison of Raman spectra of Diphenhydramine measured by 1064 nm SERS, 785 nm SERS (MIRA DS), and XTR SERS (MIRA XTR DS).
What’s the difference between Raman and SERS? Read our blog article to find out!
«Analyze This»: Raman vs SERS… What’s the Difference?

But MIRA XTR DS can do more!

With fluorescence mitigation, 785 nm Raman can be used more generally for material identification and chemical analyses.

Microcrystalline Cellulose

Microcrystalline cellulose (MCC) is another inert excipient that is commonly used in food production and the pharmaceutical industry. When interrogated with 785 nm Raman, its fluorescence can overwhelm the Raman signal and prevent identification and mixture matching (Figure 4).

Figure 4. Comparison of Raman spectra of MCC measured by 1064 nm, 785 nm (MIRA DS), and XTR (MIRA XTR DS).
Ketchup

Measurement of analytes in ketchup is a particularly interesting application, as it is a highly colored, complex mixture. With 785 nm testing, it shows fluorescence—with 1064 nm testing, it burns. But XTR analysis carries the added benefit of signal enhancement, returning a spectrum that clearly indicates the presence of trace lycopene in ketchup—the chemical that contributes its red color (Figure 5).

Figure 5. Comparison of Raman spectra of ketchup measured by 1064 nm, 785 nm (MIRA DS), and XTR (MIRA XTR DS).
Another important application demonstrates how MIRA XTR DS can distinguish imitation honey from the pure, unadulterated form in the pursuit of fraudulent food products, and that it shows promise for quantitative analysis. MIRA XTR DS extracts Raman spectra from materials that typically show fluorescence with 785 nm excitation, this time with sufficient resolution to detect different ratios of mixtures (Figure 6).
Figure 6. Comparison of Raman spectra of pure honey (left) and imitation honey (center) measured by 1064 nm, 785 nm (MIRA DS), and XTR (MIRA XTR DS). Right: Determination of the ratio of different mixtures of pure honey with adulterants using MIRA XTR DS. (Click image to enlarge.)

A powerful laboratory in the palm of your hand

Historically, Raman users dealt with fluorescence by using instruments with a 1064 nm laser. MIRA XTR DS combines the smaller size, higher resolution, and lower power consumption of a 785 nm laser with revolutionary machine learning to eXTRact Raman from fluorescent samples. The benefits are considerable!
  • Low power 785 nm laser interrogates sensitive samples without risk of ignition or burning.
  • Compact, pocket-sized design enables true single-handed operation of the device
  • The low power consumption means longer battery life for extended field use

MIRA XTR DS: all the best of handheld Raman with virtually unlimited applications.

Find out more about MIRA XTR DS

Download free white papers and learn more on our website.

Click here!
References

[1] Christesen, S. D.; Guicheteau, J. A.; Curtiss, J. M.; Fountain, A. W. Handheld Dual-Wavelength Raman Instrument for the Detection of Chemical Agents and Explosives. Opt. Eng. 2016, 55 (7), 074103. DOI:10.1117/1.OE.55.7.074103

[2] Barat, S. A.; Abdel-Rahman, M. S. Cocaine and Lidocaine in Combination Are Synergistic Convulsants. Brain Res. 1996, 742 (1), 157–162. DOI:10.1016/S0006-8993(96)01004-9

Post written by Dr. Melissa Gelwicks, Technical Writer at Metrohm Raman, Laramie, Wyoming (USA).
Chemistry of Fireworks

Chemistry of Fireworks

by | Jun 28, 2021 | Analysis

Developed nearly two millennia ago in ancient China, fireworks are increasingly used in cultural celebrations around the world and enjoyed by nearly all ages. As one of the most entertaining forms of chemistry, fireworks appeal to our senses of sight and sound, offering a staggering variety of colors, sizes, shapes, sounds, and so on. We love to watch fireworks because they take our breath away with their magnificence and mystery.

However it is not all fun and games. The business of fireworks (and the field of pyrotechnics in general) is very serious since they should be made as safe as possible to use and also environmentally friendly. Beyond fireworks, other pyrotechnics are found in all kinds of entertainment, like in concerts, movies, and more serious applications for defense and security (e.g., safety measures like flares and signal lights).

What are fireworks made of?

Early fireworks were quite dangerous and were used for protection rather than for celebrations, and hardly resemble the ones we are now familiar with.

It all began back in Ancient China with the invention of gunpowder, which was created from a mixture of charcoal, sulfur, and saltpeter (potassium nitrate). Eventually, as new developments were made to increase the safety and predictability of using these early fireworks, experimentation with colors began and people started using them more for nonviolent purposes. Now there is an entire industry devoted to the development of all kinds of fireworks for consumers and professionals alike.

Learn more about the history of fireworks in the links below:

Glossary of Firework Terminology
The History of Fireworks
Firework History

A firework, or aerial shell as it is also known, basically consists of three main parts aside from the housing: gunpowder and an igniter to make the rocket explode, and inside of the transported capsule on the top there are small garniture pods usually called «stars» (despite being shaped like spheres or cylinders) that include various chemicals for the desired effects. Stars consist of a colorant, a fuel, an oxidizer (oxygen providing substance, e.g., chlorates or nitrates), and a binder to hold the ingredient mixture together in a compact briquette.

The industry has spent a significant amount of time in development to make fireworks explode in shapes like stars and stripes, hearts, or even more complex forms like a cartoon figure, or letters and numbers if timed correctly.

Cross-sectional diagram of a firework capsule filled with star garnitures (72) and igniter (70). [1]

Forming a rainbow of colors

The vibrant colors of fireworks come from the combustion of metal ions which make up to 20% of the components. Metals have been used to color flames even before the invention of modern fireworks (e.g. Bengal fire). Chemically speaking, these metal ions change their electronic state by heating (addition of energy) and then going back to a lower energy state before emitting light of a certain color.

Table 1. List of metals used in pyrotechnics and their colors [2].

Color

Metal

Example compounds

Red

Strontium (intense red)

SrCO3 (strontium carbonate)

Lithium (medium red)

Li2CO3 (lithium carbonate)

LiCl (lithium chloride)

Orange

Calcium

CaCl2 (calcium chloride)

Yellow

Sodium

NaNO3 (sodium nitrate)

Green

Barium

BaCl2 (barium chloride)

B3N3 (boron nitride)

Blue

Copper halides

CuCl2 (copper chloride), at low temperature

Indigo

Cesium

CsNO3 (cesium nitrate)

Violet

Potassium

KNO3 (potassium nitrate)

Rubidium (violet-red)

RbNO3 (rubidium nitrate)

Gold

Charcoal, iron, or carbon black

 

White

Titanium, aluminum, beryllium, or magnesium powders

 

Very prominent here is the yellow color from sodium which is also seen in older street lightbulbs in some countries. Unfortunately, the most vibrant colors formed are also the most toxic for the environment, like strontium (red) and barium (green). These contaminants can be measured in the air, water, and even in the soil—but more on that later.

Find out more information about how fireworks get their colors in the links below:

Pyrotechnic colorant
How Do Fireworks Get Their Glorious Colors?

Safety first

Safety is always a critical issue when discussing fireworks, whether concerning their construction, their use, or their storage. Too many serious accidents have happened over the years involving fireworks.

Learn more about how to handle fireworks in a safe manner here:

Safety Tips

Among one of the largest fireworks disasters recorded in Europe was in Enschede (The Netherlands) in 2000. This explosion occurred in the warehouse of the S.E. Fireworks factory, which was located in the center of a residential area as the city grew and continued to build homes around it. An entire neighborhood was razed and the largest of the explosions was felt up to 30 kilometers away.

Because of this incident, sales of larger fireworks in most European countries is only allowed outdoors. Accumulating fireworks at home in preparation for celebrations should be avoided at least in confined environments like basements or apartments. It is better to store them in a ventilated shed or car parking to avoid problems in the case of a fire. Also do not store fireworks for long periods, since most of commercial fireworks are meant to be used within 3–6 months after production because the paper contents can get humid, ionic substances can dissolve and recrystallize, and therefore the likelihood of a failure increases.

In the event of a firework failure: Never have a look immediately! Wait at least 15 minutes at a proper distance and then use a tool to confine it afterwards—never touch it with your bare hands, especially when dealing with exploding fireworks or rockets.

Having said this, fireworks have integrated some safety features over the last several years to work more properly and reliably. For instance, the propellants have been modified from containing black powder to using technology from rockets such as plasticizers for better burning performance during launch, also resulting in less smoke and dust on the ground. A dedicated chain of reactions has to be followed, otherwise it will burn in a harmless way.

Knowledge is power: Prevent accidents with proper analytical testing

In order to help prevent fireworks accidents such as the one in Enschede and countless others, it is crucial to closely monitor different quality parameters including the water content of paper-based fireworks, grain size of the metal particles, and the purity and composition of the colorant, just to mention a few. Adequate quality control provides an entertaining, but safe fireworks experience even in the hands of the general public, when proper protocols are followed.

Metrohm offers several analytical technologies and related applications for this area of research. Analyses can be performed for a wide variety of substances and quality parameters as well as trace materials in the laboratory, on the street, and in the air either via wet chemical methods (e.g., Karl Fischer titration, ion chromatography, voltammetry) or spectroscopic techniques (e.g., near-infrared spectroscopy [NIRS] and Raman spectroscopy).

As mentioned earlier, moisture is an important quality parameter when discussing the safety of explosive materials. Metrohm offers two different techniques for accurate analysis of water content in a variety of matrices which are outlined in the following blog posts.

«Analyze This»: Moisture Analysis – Karl Fischer Titration, NIRS, or both?
«Analyze This»: Moisture analysis in ammonium nitrate

When it comes to determining the individual concentrations of the main constituents, some wet chemical techniques really stand out. Suppressed anion chromatography is ideal for measuring the ionic components of e.g., firecracker powder, other explosive material, and even in explosion residues for forensic purposes. Coupling an ion chromatograph to a mass spectrometer (IC-MS) opens up even more analysis possibilities. Read more about these studies (and more) by downloading our free Application Notes.

Chlorate, nitrate, and perchlorate in firecracker powder
Ten anions in an extract of explosives
Forensic examination analysis with IC – Determining low concentrations of chlorate, thiosulfate, thiocyanate, and perchlorate beside major anions in explosives and explosion residues

The use of several different metal salts to create the vibrant colors of fireworks can be beautiful but also harmful to our health and that of our environment. Voltammetry (VA) is an electrochemical method suitable for the determination of trace and ultratrace concentrations of heavy metals and other electrochemically active substances. Not only is VA excellent at determining these substances in the laboratory, but also in the field such as for measuring the after effects of a fireworks display or an undesired event. Check out our selection of VA instruments and applications on our website.

Metrohm: Experts in voltammetric analysis

Spectroscopic techniques like Raman can help to determine the presence of dangerous explosive materials even when keeping a safe distance by using different instrument attachments. Read our free White Paper about how to use MIRA DS from Metrohm Raman for the purpose of identifying explosives safely.

Creating Custom Libraries Detection of Binary Explosives with Mira DS

Environmentally friendly fireworks – a contradiction?

Although fireworks are a very spectacular form of entertainment, there is quite an environmental impact after big cultural events or national holidays. The general atmospheric pollution after a fireworks display has been set off can be seen in an increase of dust and smoke, but also heavy metal content in the air as most contemporary fireworks use these for coloring.

The unburnt material still contains a significant amount of heavy metals. After falling to the ground, this material can dissolve and enter the ground water after it rains. Plastics materials that covered the fireworks for safety reasons are found again as broken shell shrapnel or as microplastics. The combustion of the compounds inside the fireworks leads to increased air pollution in form of aerosols that can be measured and evaluated resulting in heavy metals in the air, fine dust, and even nanoparticles which are extremely harmful for our lungs.

Metrohm Process Analytics has developed the 2060 MARGA (Monitor for AeRosols and Gases in ambient Air) which is used by official agencies and research bodies worldwide to monitor the air quality fully autonomously. This instrument is based on the analytical technique of ion chromatography and can be used as a dedicated continuous air monitoring device that can be left unattended for several weeks at a time, or as a research instrument that can be used for other projects when not monitoring the air quality.

Learn more about the 2060 MARGA and its capabilities in our blog post.

«Analyze This»: 2060 MARGA

To find out more about the use of Metrohm instruments to monitor the air quality, check out this selection of peer-reviewed articles.

Air monitoring with ion chromatography: An overview of the literature references
The effects of firework regulation on air quality and public health during the Chinese Spring Festival from 2013 to 2017 in a Chinese megacity

A new «green» firework generation is being developed for both professional and indoor use to try to minimize the heavy metal content and also reduce aerosol forming agents. This makes them more suitable for indoor pyrotechnic shows and for movie production. In regular outdoor shows (e.g. at theme parks), the gunpowder for transport of the capsule has mostly been substituted with an air pressure gun mechanism.

A significant amount of research has gone into substituting heavy metal-based colorants with more environmentally benign substances by increasing the luminosity of lithium derivatives by substituting them for strontium, or by using boron instead of barium or chlorinated compounds.

Overview of Green Pyrotechnics (in German)

Finally, the plastic parts commonly used to surround fireworks are planned to be substituted by microcrystalline cellulose mixtures with better plasticizing binders. This leads to a similar stability compared to the current plastic materials, but the cellulose-based containers burn up completely and do not leave harmful materials scattered on the ground.

The future of fireworks shows

All safety measures increase the joy of fireworks not only during, but also after the event—being green and being safe. Foretelling the future, some of these celebrations may now use a cadre of lighted drones in a choreographed dance. This has been happening more steadily as drones fall in price and increase in their handling and programming capabilities. However, fireworks have already been with us for a couple of thousand years, and probably will not disappear any time soon.

Download our free Application Notes

and White Papers related to explosives and propellants

Metrohm Application Finder

Post written by Dr. Norbert Mayr (Ph.D. in the field of HEDM, pyrotechnics, propellants, and oxidizers), Marketing Specialist & Product Training at Metrohm International Headquarters, Herisau, Switzerland.

Real World Raman: Simplifying Incoming Raw Material Inspection

Real World Raman: Simplifying Incoming Raw Material Inspection

by | Mar 29, 2021 | Analysis

Raw material identification and verification (RMID) is a complicated process for a very important reason: it confirms the quality of the raw materials used in the manufacture of products that you put on and in your body. The complexity of RMID spans the spectrum from analytical techniques and instruments to the testing process, then to the governmental norms and standards that regulate all aspects of RMID including system suitability, extent of sampling, method validation, electronic records, and many others.

With Mira P and Mira Cal P, Metrohm Raman simplifies RMID.

Warehouse verification of incoming materials with mobile Raman in regulated industries involves performing RMID directly at the loading dock. Therefore, chemical analyses that historically would be performed in a laboratory by trained chemists can now be performed very quickly and with great success by nontechnical professionals.

Beginning with System Suitability…

Producers of handheld Raman instruments for RMID must provide suitable calibration and validation routines. Calibration of Mira P with the Calibrate/Verify Accessory (CVA) accomplishes instrument calibration as well as system and performance verification, then summarizes these tests in the System Suitability Test (SST) report for Mira P. CVA ensures that Mira P performs as intended and that users can trust in the generated data quality. Upon completion of the SST, users are assured that all measurements are in accordance with agreed standards.

For more information about instrument calibration, system verification, and performance validation for Metrohm Instant Raman Analyzers (Mira), download our free White Paper!

Metrohm White Paper: AIQ for Mira analyzers

Moving on to Sampling Flexibility…

RMID methods must accommodate a number of factors to create the most accurate and robust solution for the task. Specific consideration must be given to:

  1. The sampling strategy: how to collect the best quality data, given specific conditions
  2. Sample presentation: including morphology, packaging, and chemical nature

Handheld Raman is recognized as a particularly well-suited technique for RMID, as it offers portable, onsite, no-contact analysis of solid and liquid samples.

RMID for Regulated Industries Part I: General Considerations outlines basic applications of handheld Raman, including sampling considerations and types of evaluation. Metrohm Raman simplifies sampling with Smart Tips for every sample type.

Download RMID for Regulated Industries Part I: General Considerations

Followed by Method Development…

From Training and Validation Set building and specific recommendations for collecting best quality spectra to dedicated software routines that automatically determine optimal model parameters, Mira P streamlines development of methods for RMID with handheld Raman.

Download RMID for Regulated Industries Part II: Method Development
Download RMID for Regulated Industries Part III: Method Robustness and Validation

Successful development of a method relies on the inclusion of spectra in libraries and training sets used for RMID. Careful planning in the design phase of the model leads to an easy data collection phase. This data can then be used to determine the best model parameters for robust method development. With Mira Cal P and ModelExpert, even non-technical users can implement accurate, effective RMID methods.

Download our free Application Note AN-RS-031 for more information about Simplified RMID Model Building with Mira Cal P and Model Expert!

Simplified RMID Model Building: Mira Cal P and Model Expert

And Method Implementation…

Implementation of handheld Raman in RMID, where the majority of materials testing is performed in the receiving area, is a logical step for such a powerful technique. It has become widespread due to some very real advantages.

Massive time savings: acquisition times of less than a minute, coupled with instant, obvious results, permits very high-throughput

Faster turnaround: delivers materials to production sooner

Reduced resources: less demand for laboratory and warehouse personnel and lab consumables, costs, and workloads

Guided Workflows: predefined workflows on Mira P make sampling simple and efficient

Download RMID for Regulated Industries Part IV: Method Implementation

With Full Compliance and Utter Confidence.

Just as Mira P has built-in routines to ensure instrument integrity, Mira Cal P is designed to protect customer data integrity and simplify compliance with worldwide norms and standards. All RMID customers require data to be complete, consistent, and accurate, and MiraCal P goes beyond this with full transparency and traceability.

MiraCal P analytical software from Metrohm Raman gives you peace of mind, as it ensures all data processing adheres to several standards. More information about data integrity can be found in our free flyer.

Peace of mind with Mira Cal P – Compliance with the Data Integrity Guidelines made easy

RMID is a complex process. Learn more about how handheld Raman can provide the simplest, most efficient and accurate RMID experience possible.

Learn more about

Handheld Raman spectrometers and SERS analyzers for the lab and the process

Click here!

Post written by Dr. Melissa J. Gelwicks, Applications Chemist, Metrohm Raman, Laramie, Wyoming, USA.

Recipes with Raman

Recipes with Raman

by | Feb 22, 2021 | Analysis, Fundamentals

Many of us have spent more time in the kitchen in the past year than usual, (re)discovering our culinary skills with varying degrees of success. Our pantries have been kept full, and our stoves on for a year (and counting) since our normal, social ways of life have been curtailed by home office regulations, online schooling, and the sweeping closures of bars and restaurants.

Cooking at home can mean a number of things. Some people rely on «Chef Mike» (i.e., the microwave) to prepare their meals, while others turn humble ingredients into haute cuisine dishes. However, most people would probably agree that the keys to delicious and nutritious meals are fresh, high quality ingredients.

What is on your menu today? For breakfast, perhaps toast and some fresh pressed orange juice, lunch is maybe a quiche with tomatoes and cheese, and for dinner, stir-fried vegetables accompanied by a glass of good wine. Hungry yet?

With all of this talk about food, how can you be certain that the ingredients you are using in the kitchen are of the highest quality? You may trust in the grocery store, the brand, or the farmer at your local market, but do you know how different food quality parameters are measured?

One technique provides rapid, non-destructive and specific food quality testing: Raman spectroscopy. Whether you are looking to determine the ripeness of fruits or vegetables, the adulteration of spices or dairy products, or contamination of foods with banned pesticides, Raman spectroscopy is at the cutting edge of food quality analysis.

If you want to refresh your knowledge about Raman spectroscopy, have a look at our previous blog post about Mira, which includes some history about the technique.

«Analyze This»: How Mira Became Mobile

To learn more about the analysis of trace adulterants in foods and beverages, read our blog post all about measurement with SERS (surface‐enhanced Raman scattering).

«Analyze This»: Combat food fraud: Meet Misa

Are you confused about the differences between Raman spectroscopy and SERS? You’re not alone! Check out our blog post about these two techniques and learn about their benefits.

«Analyze This»: Raman vs SERS… What’s the Difference?

Here, we share a selection of peer-reviewed articles from the scientific community using Raman spectroscopy and portable instrumentation from B&W Tek, a Metrohm Group Company and Metrohm Raman to address quality issues of food. Enjoy your meal! Bon appetit!

~~ Starter ~~

To begin, maybe you would be interested in sharing a bottle of red wine with your companion as you snack on some crispy bread sticks. Red wines are made from red varieties of grapes, whose color is imparted through the crushing process as the skins soak in the sugary juices. Phenolic compounds derived from the grape skins can be beneficial to human health, and can be determined with Raman spectroscopy [1].

It’s not only beneficial compounds but also harmful contaminants that can be measured in beverages with Raman spectroscopy. Fungicides can also be detected in wine with SERS. Download our free Application Note if you want to find out more.

Trace Detection of Pyrimethanil in Wine with Misa

Watch our video below to see how methanol in alcoholic drinks is quantified rapidly without sample preparation – right at the bottle!

Snacking on prepackaged foods when you are on the go, or when you don’t feel like cooking at the moment, is something we have all done. The moisture levels in most of these foods is kept to a minimum, especially in those meant to have long shelf lives. Water content above certain levels allows harmful bacteria to grow, which is one of the major reasons to always consult the date of packaged foods before consumption. Eating contaminated foods can cause severe sickness and even death. It is possible to determine whether such low moisture foods (LMFs) contain harmful levels of these bacteria with SERS [2].

What else do both of these applications have in common? Both of them utilize the portable i-Raman Plus instrument from B&W Tek. For more information, download our free application note: Portable Raman for Quantification of Methanol in Contaminated Spirits.

Portable Raman for Quantification of Methanol in Contaminated Spirits

~~Main Course~~

Depending on what you are in the mood for, anything is possible. Some tomatoes, vegetables, spices, perhaps meat (if you eat it) and a starch are on the menu today, ready to be turned into almost any dish.

Determining whether fresh foods are at peak ripeness can be a tricky process, not necessarily just the change of a color. The ripeness of a fruit or vegetable indicates its antioxidant content, as well as nutrients and other beneficial compounds. Monitoring the ripening process is possible with portable Raman spectroscopy [3], such as the B&W Tek i-Raman Pro.

Some of us like a little heat in our meals. Unfortunately, the adulteration of spices like chili powder (sometimes known as cayenne powder) is common, as cheap and harmful coloring agents are added to achieve more profits at the cost of human health. These synthetic dyes are able to be determined easily even at trace levels with SERS [4].

Download our free Application Note to learn more about the detection of trace levels of Rhodamine B in cayenne powder with SERS.

Trace Detection of Rhodamine B in Cayenne Powder with Misa

Some types of cheese command a high price for what seems like just a small pinch. One such type is Parmigiano Reggiano, an Italian cheese with a protected denomination of origin (PDO) quality marker, made in compliance with several production rules. These cheeses are subject to counterfeiting, but luckily this is easy to determine on-site without damaging the sample using handheld Raman spectroscopy [5].

The price of meat varies according to several reasons, even for the same animal source, section (cut), and portion size. Among these is the origin of the meat, as well as how it was produced (e.g., organic or a factory farm). Determining the difference between premium meat products and lower quality ones is possible with handheld Raman systems [6] such as Mira from Metrohm Raman. Not only these differences but also the freshness of meat during the production process can be measured with portable Raman devices [7] like the i-Raman Plus from B&W Tek.

Using lower quality cooking oil with a low smoke point at high temperatures can result in consumption of harmful byproducts formed during cooking. Older oils have a lower antioxidant content as a result of the aging process, and can become rancid when the antioxidant properties vanish. For these reasons, high quality edible oils full of antioxidants are worth much more, but are also susceptible to adulteration with cheaper ingredients. It is possible to not only determine the purity of edible oils by Raman spectroscopy [8] but also the heat stability of different types of oils [9].

For more information about the analysis of edible oils by Raman spectroscopy, download our free Application Notes and our White Paper below!

Fast Ingredient Analysis of Edible Oils Using a Portable Raman Spectrometer
Trace Detection of Fenthion in Olive Oil with Misa
White Paper: Facile Verification of Edible Oils with Raman Spectroscopy

~~ Dessert ~~

After dinner is over, a hot beverage like tea can be nice to cleanse the palate. How can you be sure that the tea is free of banned pesticides, other than buying from a trusted organic label? SERS allows rapid identification of such substances in tea leaves [10].

To learn more about detecting illegal compounds such as herbicides on tea leaves, download our free Application Note.

Trace Detection of Paraquat in Tea Leaves with Misa

The honey you put in your tea or drizzle over your dessert can also be subjected to tampering. Depending on the type of flower or the origin of the honey, costs can vary widely for the same volume. Some honeys (e.g., Manuka) claim to impart certain health benefits, and therefore many lower quality products with cheap sweeteners (e.g., high fructose corn syrup) are falsely labeled as such and sold at a higher price point to unsuspecting consumers. It is possible to detect honey adulteration [11] and even its botanical origin [12] with Raman spectroscopy.

Not only tea and honey, but also coffee and the milk added to it can be analyzed with Raman spectroscopy to determine various quality markers and adulterants.

The protein content of milk can be falsely enhanced with the addition of melamine. This compound is now monitored in dairy products due to scandals which led to deaths from kidney damage. Melamine [13] and other substances which can contribute to ill health effects [14] can be easily determined in milk with SERS.

Want to learn more about Melamine and how to measure it with SERS? Check out our free Application Note for further information.

Trace Detection of Melamine in Dairy Products with Misa

Download our free Application Note to learn about the rapid detection of the alkaloid trigonelline in coffee, which reduces in concentration the darker the beans are roasted.

Fast and Selective Detection of Trigonelline Coffee Quality Marker

The ripeness of fruits and vegetables is not just important information when planning meals, but it is also critical for food transport. Perishable fruits and vegetables are often shipped in an unripened state so they arrive at their destination in top condition.

Freshness in citrus fruits can be determined with portable Raman instruments by measuring the carotenoid content [15].

Aside from the freshness, it is also possible to detect if pesticides, fungicides, herbicides or other harmful substances have been sprayed onto fruits using SERS [16].

Check out our selection of free Application Notes below about the determination of these kinds of substances on different fruits with Misa.

Trace Detection of Thiram on Apples
Trace Detection of Carbendazim on Strawberries
Trace Detection of Thiabendazole on Bananas

Several food quality parameters can be measured quickly and easily with Raman spectroscopy without the need to open bottles or destroy samples. Portable and handheld instruments make measurements simple to perform nearly anywhere. Visit the Metrohm website to learn more about the possibilities with Raman!

Learn more about rapid food analysis with Raman spectroscopy

Download free applications directly from our website.

Click here!

References

[1] Dranca, F.; Oroian, M. Kinetic Improvement of Bioactive Compounds Extraction from Red Grape (Vitis vinifera Moldova) Pomace by Ultrasonic Treatment. Foods 2019, 8, 353. doi:10.3390/foods8080353

[2] Pan, C.; Zhu, B.; Yu, C. A Dual Immunological Raman-Enabled Crosschecking Test (DIRECT) for Detection of Bacteria in Low Moisture Food. Biosensors 2020, 10, 200. doi:10.3390/bios10120200

[3] Trebolazabala, J.; Maguregui, M.; Morillas, H.; et al. Portable Raman spectroscopy for an in-situ monitoring the ripening of tomato (Solanum lycopersicum) fruits. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2017, 180, 138–143. doi:10.1016/j.saa.2017.03.024

[4] Lin, S.; Hasi, W.-L.-J.; Lin, X.; et al. Rapid and sensitive SERS method for determination of Rhodamine B in chili powder with paper-based substrates. Analytical Methods 2015, 7, 5289–5294. doi:10.1039/c5ay00028a

[5] Li Vigni, M.; Durante, C.; Michelini, S.; et al. Preliminary Assessment of Parmigiano Reggiano Authenticity by Handheld Raman Spectroscopy. Foods 2020, 9(11), 1563. doi:10.3390/foods9111563

[6] Logan, B.; Hopkins, D.; Schmidtke, L.; et al. Authenticating common Australian beef production systems using Raman spectroscopy. Food Control 2021, 121, 107652. doi:10.1016/j.foodcont.2020.107652

[7] Santos, C; Zhao, J.; Dong, X.; et al. Predicting aged pork quality using a portable Raman device. Meat Science 2018, 145, 79–85. doi:10.1016/j.meatsci.2018.05.021

[8] Liu, Z.; Yu, S.; Xu, S.; et al. Ultrasensitive Detection of Capsaicin in Oil for Fast Identification of Illegal Cooking Oil by SERRS. ACS Omega 2017, 2, 8401–8406. doi:10.1021/acsomega.7b01457

[9] Alvarenga, B.; Xavier, F.; Soares, F.; et al. Thermal Stability Assessment of Vegetable Oils by Raman Spectroscopy and Chemometrics. Food Analytical Methods 2018, 11, 1969–1976. doi:10.1007/s12161-018-1160-y

[10] Yao, C.; Cheng, F.; Wang, C.; et al. Separation, identification and fast determination of organophosphate pesticide methidathion in tea leaves by thin layer chromatography–surface-enhanced Raman scattering. Analytical Methods 2013, 5, 5560. doi:10.1039/c3ay41152d

[11] Li, S.; Shan, Y.; Zhu, X.; et al. Detection of honey adulteration by high fructose corn syrup and maltose syrup using Raman spectroscopy. Journal of Food Composition and Analysis 2012, 28, 69–74. doi:10.1016/j.jfca.2012.07.006

[12] Oroian, M.; Ropciuc, S. Botanical authentication of honeys based on Raman spectra. Journal of Food Measurement and Characterization 2017, 12, 545–554. doi:10.1007/s11694-017-9666-3

[13] Nieuwoudt, M.; Holroyd, S.; McGoverin, C.; et al. Rapid, sensitive, and reproducible screening of liquid milk for adulterants using a portable Raman spectrometer and a simple, optimized sample well. Journal of Dairy Science 2016, 99, 7821–7831. doi:10.3168/jds.2016-11100

[14] Lin, X.; Hasi, W.-L.-J.; Lou, X.-T.; et al. Rapid and simple detection of sodium thiocyanate in milk using surface-enhanced Raman spectroscopy based on silver aggregates. Journal of Raman Spectroscopy 2014, 45, 162–167. doi:10.1002/jrs.4436

[15] Nekvapil, F.; Brezestean, I.; Barchewitz, D.; et al. Citrus fruits freshness assessment using Raman spectroscopy. Food Chemistry 2018, 242, 560–567. doi:10.1016/j.foodchem.2017.09.105

[16] Xie, J.; Li, L.; Khan, I.; et al. Flexible paper-based SERS substrate strategy for rapid detection of methyl parathion on the surface of fruit. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2020, 231, 118104. doi:10.1016/j.saa.2020.118104

Post written by Dr. Sara Seiffert (Product Specialist Spectroscopy at Metrohm Deutschland) and Dr. Alyson Lanciki (Scientific Editor at Metrohm International Headquarters).