Liquid Chromatography-Mass Spectrometry
Liquid Chromatography–Mass Spectrometry (LC-MS) is the coupling of two highly useful techniques. LC involves chemical separation by pumping eluents through a solid medium (column), paired with precise mass-to-charge identification of the separated chemicals by the mass spectrometer, which serves as the detector. The combination of these techniques is highly effective for high-throughput identification in environmental monitoring, food safety testing, drug discovery and development, and clinical diagnostics.
Analytes from complex matrices found in drug discovery, clinical screening, or environmental testing can be isolated using Solid Phase Extraction (SPE). This is followed by LC separation with stationary phases - such as reversed-phase, ion-exchange, or size-exclusion - selected based on the analytes’ chemical characteristics and molecular size. The mass spectrometer then identifies and quantifies the analytes, enabling drug level monitoring, therapeutic range determination, pollutant detection, toxicological analysis, and food contaminant screening.
How Hamilton Supports Your LC-MS Workflows
Hamilton provides complete LC-MS support, from fully automated sample preparation to manual injection tools. Workstations like the MassSTAR, Dual MassSTAR, and MassXtract automate critical steps such as protein precipitation and SPE, improving consistency and throughput. For manual or lower-throughput labs, the Microlab Diluter-Dispenser streamlines tasks like serial dilutions, calibration standard prep, and reagent addition, minimizing variability and solvent exposure. Hamilton also offers high-precision HPLC syringes for both manual use and autosamplers, with gas-tight, low-carryover performance.
For chromatographic separation, Hamilton supplies anion and cation exchange resins for highly polar analytes like proteins and oligonucleotides, along with robust reversed-phase columns built on a 55% crosslinked PS-DVB structure for exceptional stability across all pH levels and temperatures up to 100 °C.
Explore our LC-MS Solutions and Applications in Detail
Automated workstation
BIOSPOT® Workstation
Lab Syringes
Gastight Syringes
Manual GC and HPLC Syringes
HPLC Manual Injection
Syringes for HPLC Autosamplers
Syringes for Agilent HPLC Autosamplers
Syringes for HPLC Autosamplers
CTC/LEAP PAL HPLC Autosampler Syringes
Syringes for HPLC Autosamplers
Syringes for Antec HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Spectra Physics ThermoFinnigan HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Waters HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Dionex HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Hitachi HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Spark Holland HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Shimadzu HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Bruker Varian HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Beckman Coulter HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Grace Alltech HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Kontron HPLC Autosamplers
Syringes for HPLC Autosamplers
Syringes for Perkin Elmer HPLC Autosamplers
Benchtop & Handheld Solutions
Diluter Dispensers
Diluter Dispensers
Microlab 600 Diluters
Diluter Dispensers
Microlab 600 Dispensers
Available Hamilton Methods
Good to Know About LC-MS Workflows
This section provides a selection of additional resources related to the application described on this page. It includes helpful articles, videos, and blogs that offer deeper insights into the topic.
Useful Links
External resources not written by Hamilton but valuable for understanding the topic, such as industry guidelines, explanatory videos, or relevant tools.
| LC-MS/MS Fundamentals - Chromatography Online | Watch Video |
| Liquid Chromatography-Mass Spectrometry || Basic Principles - HPLC Professionals | Watch Video |
| Stoll, D. R. (2023). Initiating method development with scouting gradients—Where to begin and how to proceed? LCGC North America, 41(5), 160–165. | Read Article |
| Chromatography Online - LCGC International | Visit Website |
Scientific Articles
Peer-reviewed journal publications that feature Hamilton products, demonstrating their use in real-world research and application
| Ory, D., Van den Brande, J., de Groot, T., Serdons, K., Bex, M., Declercq, L., Cleeren, F., Ooms, M., Van Laere, K., Verbruggen, A., & Bormans, G. (2015). Retention of [¹⁸F]fluoride on reversed phase HPLC columns. Journal of Pharmaceutical and Biomedical Analysis, 111, 209–214 | Read Article |
| Sreekanta Nath Dalal, Md Jabir Rashid and Md Sakil Amin. Development of a simple RP-HPLC method for the determination of EDTA residue in pharmaceutical clean-in-place (CIP) applications. International Journal of Science and Research Archive, 2025, 14(03), 1459-1464. | Read Article |
Hamilton Products in Action
A collection of videos showcasing Hamilton products in use, providing practical insights into their functionality and benefits.
Solutions for the Top 3 Challenges in Liquid Chromatography - Mass Spectrometry
Ensuring Sample Purity for Accurate Mass Spectrometry
Challenge: Impurities and inconsistent cleanup can compromise mass spectrometry by distorting results and masking analytes of interest.
Solution: Hamilton MassSTAR, Dual MassSTAR, and MassXtract platforms fully automate sample preparation, including SPE and protein precipitation to ensure high sample purity. These systems reduce manual variability and deliver clean, isolated targets for improved generation of mass spectra.
Volatile compounds in environmental testing
Challenge: Detecting volatile or temperature-sensitive pollutants in environmental samples, such as those found in indoor air or water, requires highly stable and controlled sample preparation, particularly prior to LC-MS or HPLC analysis.
Solution: Hamilton automated liquid handlers provide accurate sample preparation and dilution workflows compatible with both LC-MS and HPLC systems. For workflows involving volatile compounds, the use of temperature control modules (e.g., sample cooling carriers, cooled reagent carriers) helps preserve sample integrity during processing. These tools are ideal for liquid extractive methods, ensuring reproducible results across various environmental matrices. With Hamilton modular, chromatography-compatible solutions, labs can confidently detect trace-level pollutants with minimal sample loss or degradation.
Separation of Highly Basic Compounds
Challenge: Traditional silica-based columns degrade at high pH, especially above pH 10, where basic compounds like amines and nitrogen-containing drugs are mostly uncharged. Under these conditions, silica surfaces undergo bonded phase stripping, exposing reactive silanol groups. This leads to peak tailing, poor efficiency, and permanent damage to the stationary phase.
Solution: Hamilton’s PRP-1 column, built on a poly (styrene-divinylbenzene) (PS-DVB) backbone, contains no silica core, which eliminates silanol-related interactions. The column's chemically inert structure remains stable from pH 0 to 14, delivering sharp, symmetric peaks even for highly basic analytes at alkaline pH (>11).
Contamination can be reversed: the phase tolerates aggressive cleaning with strong acids or bases, allowing full regeneration and extended column life.
What is LC-MS used for?
LC-MS is one of the most versatile tools in modern analytical science. It combines the separation power of liquid chromatography with the precision of mass spectrometry, enabling both quantitative and qualitative analysis of complex samples. LC-MS is widely used across pharmaceutical research, clinical diagnostics as well as environmental and food safety testing. Its high sensitivity, specificity, and throughput make it the gold standard for detecting compounds at trace levels in many applications.
LC-MS is also essential for applications that require strict regulatory compliance, such as therapeutic drug monitoring (TDM) and toxicology testing. By integrating solid phase extraction (SPE) with automated workflows, LC-MS ensures cleaner samples, improved reproducibility, and reduced human error. These advantages make LC-MS a cornerstone technology for laboratories focused on accurate, high-throughput testing.
Purpose: Used to measure drug concentrations in blood or plasma to guide dosage, ensuring patients receive safe and effective levels of medication.
Drugs commonly monitored: Tacrolimus, sirolimus, everolimus, vancomycin, carbamazepine, clozapine, imatinib, etc.
Why LC-MS? Its superior accuracy, sensitivity, and ability to distinguish structurally similar compounds make it indispensable in clinical settings. LC-MS can detect therapeutic ranges for drugs with narrow safety margins, helping clinicians make precise, data-driven decisions.
Learn more on our TDM application page.
Purpose: Detect and quantify drugs of abuse, toxins, and overdoses in clinical, forensic, or workplace settings.
Applications:
- Clinical toxicology (e.g. ER testing)
- Forensic toxicology (e.g. postmortem analysis)
- Workplace drug testing
Why LC-MS? Its broad compound coverage, low detection limits, and unmatched specificity ensure accurate results, even in complex biological samples.
Learn more on our Toxicology application page.
Purpose: Study of small-molecule metabolites in biological systems.
Applications:
- Disease biomarker discovery
- Personalized medicine
- Nutritional and microbiome research
Why LC-MS?: It offers sensitive detection of a wide range of metabolites, including those present at very low concentrations, making it crucial for systems biology and precision medicine.
Purpose: Identification and quantification of proteins and peptides.
Applications:
- Biomarker discovery
- Characterization of post-translational modifications
- Biotherapeutic development
Why LC-MS? LC-MS is essential in proteomics and peptidomics because of its ability to sensitively and precisely identify, characterize, and quantify proteins and peptides, often in highly complex mixtures such as blood, tissue, or cell lysates.
Learn more on our Protein Science application page.
Purpose: Measure drug absorption, distribution, metabolism, and excretion.
Applications:
- Preclinical and clinical drug development
- Bioequivalence studies
Why LC-MS? It allows accurate quantification of drugs and their metabolites over time, which is essential for understanding dosing and efficacy.
Learn more on our DMPK application page.
Purpose: Early detection of congenital conditions
Analytes: Amino acids, acylcarnitines, organic acids.
Sample type: Dried blood spots.
Why LC-MS?: High-throughput, multiplexed detection in a single run allows for faster results and early intervention in critical conditions.
Purpose: Measurement of hormones like testosterone, estradiol, cortisol, etc.
Applications:
- Clinical Diagnostics and Endocrinology
- Reproductive and Hormone-Sensitive Conditions
- Stress, Psychiatry, and Behavioral Research
- Sports Medicine and Anti-Doping
- Pharmaceutical and Veterinary Research
Why LC-MS? It provides greater specificity and accuracy compared to immunoassays, especially at low levels or in pediatric populations
Purpose: Detect contaminants such as pesticides, mycotoxins, veterinary drugs, and industrial pollutants.
Examples: LC-MS is used to ensure food and water safety, especially for regulatory compliance.
Why LC-MS? It provides exceptional sensitivity, specificity, and the ability to handle complex samples with trace-level contaminants.
LC-MS Case Studies and Application Notes
OtherLC-MS Resources
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
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