Mass Spectrometry Characterization Services

Detect and identify unknowns, mixtures, chemical structures, and more…

Mass spectrometry (MS) is a versatile tool useful for characterizing a wide range of materials. Its ability to provide molecular and elemental information with high sensitivity makes it applicable across numerous fields. Here are some of the materials that Triclinic Labs has used MS to effectively characterize:

Material	Use	Examples
Small Molecules (Pharmaceuticals, Organic Compounds)	MS can analyze the molecular structure, purity, and composition of small organic molecules, including active pharmaceutical ingredients (APIs), metabolites, and degradation products.	Drugs, pesticides, pollutants, and synthetic chemicals.
Polymers and Coatings	MS can determine molecular weight distribution, polymer composition, cross-linking, degradation, and the presence of additives, plasticizers, or impurities. Techniques like Matrix Assisted Laser Desorption (MALDI-MS) and Electrospray Ionization (ESI-MS) are often used.	Polyethylene, polyesters, latex paints, varnishes.
Biomolecules (Proteins, Peptides, Lipids, Nucleic Acids)	Mass spectrometry (especially MALDI-MS) and Liquid Chromatography (LC-MS/MS) are crucial for identifying and quantifying biomolecules. It helps in proteomics for protein identification, post-translational modification studies, and lipidomics for lipid profiling.	Proteins, DNA/RNA, lipids, and carbohydrates.
Natural Products	MS is employed to characterize complex mixtures of natural compounds, determining molecular weights and structures of unknown molecules in natural product research.	Supplements, plant extracts
Metals and Inorganic Materials	Mass spectrometry, particularly Inductively Coupled Plasma Mass Spectrometry (ICP-MS), is widely used for elemental and isotopic analysis in inorganic materials. Click here for a full description of ICP MS.	Metal alloys, nanomaterials, environmental samples (water, soil), and geological samples.
Petroleum Products	MS can identify complex mixtures of hydrocarbons and other compounds in crude oil and refined petroleum products, essential for petroleum refining and quality control.	Crude oil, gasoline, diesel, lubricants.
Food and Beverages	MS helps detect contaminants, additives, and nutritional compounds, as well as perform quality control and adulteration detection in food products.	Vitamins, preservatives, flavor compounds, and contaminants like pesticides.
Cosmetic and Personal Care Products	MS can be used to analyze the composition of cosmetic ingredients, including fragrances, preservatives, and colorants.

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Applications in pharmaceutical small molecule development.

LC-MS is a powerful analytical tool widely used in small molecule drug development. Its versatility allows for the detection, identification, quantification, and structural elucidation of compounds. Here are some typical applications of mass spectrometry in small molecule drug development that we offer:

1. Quantification of Active Pharmaceutical Ingredients (APIs)

• Application: LC-MS can accurately quantify the amount of API in a drug formulation.
• Importance: This is essential for ensuring the correct dosage in each formulation batch.

2. Impurity Profiling and Degradation Studies

• Application: LC-MS helps in detecting and quantifying impurities or degradation products in drug formulations. Rule out the presence of a contaminant, a cytotoxic component, surfactant residues or other unwanted analyte.
• Importance:Regulatory agencies require thorough impurity profiling to ensure drug safety.

3. Structure Elucidation

• Application: LC-MS/MS (tandem mass spectrometry) is employed to elucidate the chemical structure of small molecules and their fragments.
• Importance: Helps in identifying unknown compounds, metabolites, or degradation products during drug development.

4. Chiral Analysis

• Application: LC-MS helps in the separation and quantification of enantiomers of chiral drugs.
• Importance: It's critical to differentiate between enantiomers since one may be therapeutically active while the other may cause adverse effects.

5. Formulation Development and Stability Testing

• Application:LC-MS is used to assess the stability of a drug substance or formulation over time and under different conditions.
• Importance: Ensures that the drug maintains its efficacy and safety throughout its shelf life.

6. Metabolite Identification

• Application: LC-MS is essential in identifying and characterizing drug metabolites during preclinical and clinical phases.
  
• Importance: Understanding how a drug is metabolized is critical for assessing potential drug-drug interactions, safety, and efficacy.

7. Extractables and Leachables (E&L)

• Extractables and Leachables (E&L) testing is a critical part of pharmaceutical and medical device development, ensuring that potentially harmful substances are not leached into drug products from packaging or container materials. The techniques used for E&L testing typically fall into the following categories:

a. Extraction Techniques for Extractables Testing:

These techniques aim to identify potential extractables (chemicals that could be released under stress conditions) from materials in contact with the drug product.

• Soxhlet Extraction: Involves repeatedly washing the sample with an organic solvent at its boiling point to extract potential contaminants.
• Reflux Extraction: Similar to Soxhlet but less intensive, it uses continuous boiling and condensation of solvent to extract compounds.
• Ultrasonic Extraction: Uses ultrasonic waves in a solvent to extract materials from surfaces or pores of the container.
• Accelerated Solvent Extraction (ASE): Uses high pressure and temperature to increase the efficiency of the solvent extraction process.
• Simulated Extraction: Mimics actual use conditions, using solutions similar to the drug product (e.g., buffers, saline, or ethanol) to extract materials.

b. Analytical Techniques for Identifying and Quantifying Extractables:

These are used to analyze the materials obtained from the extraction techniques.

• Gas Chromatography-Mass Spectrometry (GC-MS): Ideal for volatile and semi-volatile organic compounds, it separates chemicals based on their volatility and provides identification and quantification.
• Liquid Chromatography-Mass Spectrometry (LC-MS): Used for non-volatile and larger molecules, this technique is ideal for analyzing complex mixtures of organic compounds.
• Inductively Coupled Plasma-Mass Spectrometry (ICP-MS): Used for detecting and quantifying metal impurities that could leach from components like glass, rubber, or plastic.
• Fourier-Transform Infrared Spectroscopy (FTIR): Identifies organic compounds based on their infrared absorption spectra and is particularly useful for polymer identification.
• Nuclear Magnetic Resonance (NMR) Spectroscopy: Helps in the identification of unknown organic compounds based on the magnetic properties of their nuclei.
• High-Performance Liquid Chromatography (HPLC): Often used for non-volatile organic compounds, separating them for analysis based on their polarity and solubility.

c. Leachables Testing:

Once extractables have been identified, testing is done under actual storage and use conditions to identify which substances leach into the drug product.

• Stability Testing: This involves testing the drug product in its final packaging over a period to assess any leachables that may appear during storage.
• Simulated Use Testing: The packaging is exposed to conditions similar to real-world use (e.g., temperature variations, different solvents) to evaluate potential leachables.
• Headspace Analysis (for volatiles): This technique assesses volatile compounds in the headspace of a closed vial or container.

d. Toxicological Risk Assessment:

Once extractables and leachables are identified, toxicologists assess their potential risk based on their chemical structure and concentration, compared with established safety thresholds (such as the Permitted Daily Exposure, or PDE).
Combining these techniques allows comprehensive E&L testing, ensuring product safety and compliance with regulatory guidelines such as those from the FDA or EMA.

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Mass Spectrometry Instrumentation and Details
(LC, GC, ICP and MALDI MS) -

Application AND Technique Description
Used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and other chemical compounds. When skillfully analyzed, MS spectra can provide important information for structural elucidation/characterization and facilitate identification of unknown compounds by comparison to mass spectral libraries. An important enhancement to the mass resolving and mass determining capabilities of mass spectrometry is using it in tandem with chromatographic and other separation techniques. A common combination is gas chromatography-mass spectrometry (GC/MS or GC-MS). In this technique, a gas chromatograph is used to separate different compounds. Similar to gas chromatography MS (GC-MS), liquid chromatography-mass spectrometry (LC/MS or LC-MS) separates compounds chromatographically before they are introduced to the ion source and mass spectrometer. It differs from GC-MS in that the mobile phase is liquid, usually a mixture of water and organic solvents, instead of gas. Mass spectrometry has both qualitative and quantitative uses. These include identifying unknown compounds, determining the isotopic composition of elements in a molecule, and determining the structure of a compound by observing its fragmentation. Other uses include quantifying the amount of a compound in a sample or studying the fundamentals of gas phase ion chemistry (the chemistry of ions and neutrals in a vacuum). MS is now commonly used to study physical, chemical, or biological properties of a great variety of compounds(e.g. large and small organic molecules and inorganics).
Instruments Used	Model	Notes:
Voyager	DE Pro (MALDI)	MALDI-TOF provides a high mass range (up to 100,000 Da), high mass resolution, and high mass accuracy. MALDI mass spectrometry applications include molecular weight determination, molecular weight distribution, protein identification and characterization, pharmaceutical characterization, and more. Samples types include polymers, lipids, oligosaccharides, phosphopeptides, and small molecules.
Agilent	6460 Triple Quad LC/MS/MS	With its high sensitivity, the 6460 Triple Quad can detect trace-level compounds, making it ideal for applications such as environmental testing, pharmaceutical research, and clinical analysis. The flexibility in ionization and detection makes it suitable for a broad range of analytical applications.
ThermoFisher Scientific	LC/MS: Orbitrap Exploris 120 MS with Vanquish LC	A high performance quadrupole Orbitrap system that combines a quadrupole, an ion routing multipole, and Orbitrap analyzer and features higher-energy collisional dissociation (HCD) and in-source fragmentation. The high field Orbitrap mass analyzer performs high-resolution accurate mass analysis, with and without HCD fragmentation. Supports fast gradient separations in LCMS workflows, UHPLC applications, and standard HPLC workflows. The system provides resolution up to 120,000 FWHM (Full Width Half Maximum), allowing for precise mass measurements with high confidence in compound identification and for distinguishing between closely related compounds and accurately identifying unknowns in complex samples.
ThermoFisher Scientific	Thermo 8000 GC/MS	Electron impact (EI) mode, utilizing a DB-5 column and thermal gradient
ThermoFisher Scientific	iCAP RQ ICP-MS	This innovative single quadrupole (SQ) ICP-MS is the ideal trace elemental analyzer for a wide range of sample types.

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