Use high-resolution mass spectrometry evidence to identify unknowns, impurities, degradants, and molecular formulas.
Use high-resolution mass spectrometry (HRMS) evidence to identify unknowns, impurities, degradants, and molecular formulas.
Use chromatographic, and high-resolution accurate-mass spectrometry data to separate complex materials, assign formulas, detect trace components, profile impurities, and support molecular structure elucidation. Chromatography to separate materials and mass spec to identify the. We offer HPLC, GC, and ICP MS services as well as semi-prep LC.
Mass spectrometry provides formula and fragment evidence
Mass-spectrometry is useful for chemical characterization, trace-level detection, molecular analysis, structure, and composition determination. It also notes that LC-MS can support small-molecule drug development through API quantitation, impurity profiling, degradation studies, structure elucidation, chiral analysis, stability testing, metabolite identification, and extractables/leachables work.
High-resolution accurate-mass data can narrow candidate formulas and provide atom-count constraints. Tandem MS fragmentation can support substructure and connectivity hypotheses, but structural assignments should be checked against orthogonal evidence when the regulatory or IP consequence is significant.
How the data fits together
Question
Useful evidence
Decision output
What is the molecular identity or formula of the molecule of interest?
LC/MS HR/MS, MS/MS fragments, NMR, elemental or isotope information where relevant.
Candidate formula and structure assignment with alternatives and limitations.
Can I obtain a crystal structure or absolute configuration?
SCXRD, MicroED, PXRD, crystallographic refinement, spectroscopy and chemistry context.
Structure solution, unit-cell or form confirmation, stereochemical interpretation when supported.
How can I determine the impurity or contaminant identity?
Chromatography, HRMS, MicroED if crystalline, NMR if sufficient material, Raman/IR, microscopy.
Root-cause-ready identity conclusion and evidence package.
How do I resolve solid-form phase or formulation ambiguity?
Phase/form assignment and control or follow-up recommendation.
When HRMS should be paired with Micro Electron Diffraction (MicroED) or NMR
The 2026 Triclinic HRMS/MicroED impurity white paper explains why impurity identification is difficult: trace quantities may require many preparative HPLC runs, and MS and NMR can provide fragmented information that may not fully solve the molecular puzzle.
Pairing HRMS with MicroED is particularly useful when the impurity crystallizes in nanoscale particles. HRMS supplies accurate m/z and candidate formula constraints; MicroED can provide crystal-structure evidence from very small crystallites.
Trace impurity structure assignment using HRMS and MicroED
Figure 1. HRMS provides accurate m/z and candidate molecular formula constraints, while MicroED can solve crystal structures from nanoscale crystallites. Together they narrow molecular possibilities when chromatography provides too little isolated material for conventional workflows. Source: George, Vanlerberghe, and Boerrigter, Molecular Structure Solution of Impurities in Liquid Chromatography Assays using Microcrystal Electron Diffraction and High-Resolution Mass Spectrometry, Triclinic Labs white paper, Q1 2026.
Examples and Publications.
These source-backed examples connect LC/MS and HR/MS Structure Support to actual Triclinic materials and peer-reviewed literature. Each example includes author, publication date, and an abstract-level explanation.
Molecular Structure Solution of Impurities in Liquid Chromatography Assays using Microcrystal Electron Diffraction and High-Resolution Mass Spectrometry
Author: Gary C. George III, Jason Vanlerberghe, and Stephan X.M. Boerrigter
Publication date: Q1 2026
Abstract: This Triclinic Labs white paper addresses a common CMC problem: impurity peaks often exist in trace quantities that make isolation and traditional structure elucidation difficult. HRMS provides accurate m/z and candidate formula constraints, while MicroED can determine crystal structures from nanoscale crystallites, making the combined workflow useful for rapid definitive impurity identification.
Integrating Microcrystal Electron Diffraction as a Mainstream Work Tool in Solid Form Development and Structure Elucidation
Author: Shawn C. Comella, Gary C. George III, and Steef X.M. Boerrigter
Publication date: Q2 2026
Abstract: This Triclinic Labs white paper explains how MicroED removes the large-single-crystal bottleneck by enabling molecular structure determination directly from sub-micron crystals. It frames MicroED as a mainstream structure-elucidation workflow when integrated with expert crystallography, PXRD, HRMS, Raman/IR, and other orthogonal methods.
The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination
Author: Christopher G. Jones, Michael W. Martynowycz, Johan Hattne, Tyler J. Fulton, Brian M. Stoltz, Jose A. Rodriguez, Hosea M. Nelson, and Tamir Gonen
Publication date: 2018
Abstract: This ACS Central Science paper reports MicroED as a route to routine and unambiguous structural determination of small organic molecules from simple powders and nanocrystals with minimal preparation. It is a useful literature anchor for why MicroED belongs in modern small-molecule structure-elucidation workflows.
Which structure elucidation technique should be used first?▾
The first technique depends on the decision, material amount, sample form, and prior data. Single-crystal X-ray diffraction is preferred when suitable crystals are available; MicroED is valuable for microcrystalline particles; NMR supports connectivity and local environment; LC/MS HR/MS supports formula and fragment evidence; Raman/IR and microscopy help connect molecular and physical identity.
Can Triclinic work with very small amounts of material?▾
Yes, many structure-elucidation workflows can be scoped around limited material, but feasibility depends on crystallinity, purity, sample matrix, detection limit, and whether the question requires definitive structure, tentative identification, or triage.
Can this work support CMC, regulatory, quality, or IP decisions?▾
Yes, if the work is scoped to the evidentiary standard required. Reports should state what the data prove, what remains ambiguous, and what additional evidence would change the conclusion.
Why use orthogonal techniques?▾
No single method answers every structural question. Orthogonal evidence reduces misassignment risk by connecting formula, connectivity, phase identity, crystal structure, purity, sample history, and matrix behavior.
Can accurate mass alone prove an impurity structure?▾
No. Accurate mass can strongly constrain elemental composition, but isomers and alternative structures may share a formula. Fragmentation, retention behavior, reference standards, NMR, or other orthogonal evidence may be required.
Discuss LC/MS HR/MS structure support
Share the material, chromatographic information, expected mass range, impurity or formula question, sample amount, matrix, and decision the data must support.
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