LC-MS Analysis | EUROLAB

What Is LC-MS Analysis?

LC-MS is a hybrid technique in which components separated by liquid chromatography are transferred to a mass spectrometer via an interface (usually electrospray ionisation). Chromatography provides separation, and mass measurement provides identification via molecular mass.

Purpose of LC-MS Analysis

The purpose is to both separate and identify non-volatile, polar or thermally labile compounds that cannot be analysed by GC. Peptides, proteins, drug metabolites and polar residues are studied with this technique.

Which Products Is LC-MS Analysis Applied To?

Pharmaceutical active ingredients and their metabolites
Drug levels in biological samples
Polar pesticide and veterinary drug residues in food
Mycotoxins
Peptide and protein characterisation

In Which Sectors Is LC-MS Analysis Used?

ChemistryPharmaceuticalsFoodCosmeticsEnvironmentBiotechnologyAgriculture

Standards Related to LC-MS Analysis

ICH Q2(R2) (validation of analytical procedures)
European Pharmacopoeia 2.2.43 (mass spectrometry)
EN 15662 (QuEChERS ekstraksiyonu)
EU 2021/808 (performance of veterinary drug residue methods)

LC-MS Analysis Conditions

ionization: ESI is common; APCI is preferred in non-polar compounds
Polarite: Positive or negative ion mode—depending on analyte
Hareketli faz: Volatile buffer required; Salts that disrupt ionization are not used
Matris etkisi: Ion suppression should be evaluated; matrix matched calibration recommended

Equipment for LC-MS Analysis

HPLC/UPLC system
Electrospray or APCI ion source
Mass analyser (single quadrupole or high-resolution)
Vacuum system and nitrogen generator
Data processing software

Sample Requirements for LC-MS Analysis

The sample must be made soluble in a volatile buffer
Must be free of salts and detergents that disrupt ionisation
Protein precipitation or SPE is applied for biological samples
The sample must be sent in the cold chain

Duration of LC-MS Analysis

A run is generally under 30 minutes. If method development and matrix-effect assessment are required, total duration extends significantly.

LC-MS Analysis Procedure

1The sample is extracted and cleaned of interfering components.
2An internal standard is added.
3Separation is performed on the LC column.
4The column outlet is fed to the ion source and components are ionised.
5The mass spectrum is recorded.
6Identification is made through agreement of mass and retention time.
7Quantitation is calculated via the internal standard.

LC-MS Analysis Acceptance Criteria

A method produces a result; it does not set a limit. Whether the result is acceptable is determined by the regulation or specification the product is subject to.

Evaluation of Results

Ion suppression is the most important source of error in LC-MS; an internal standard, and an isotope-labelled standard where possible, is therefore used. Reliability of the result depends on the matrix effect having been measured during method validation.

LC-MS Analysis Report

Sample description, receipt date and laboratory number
Method applied and reference standard, if any
Instrument and measurement conditions
Sample preparation steps
Measurement results and units
Measurement uncertainty (if requested)
A statement that the results relate only to the sample submitted for testing

Accreditation

EUROLAB holds internationally recognised accreditation obtained from accreditation bodies party to the IAF and ILAC multilateral recognition arrangements, under ISO/IEC 17025 for laboratory testing, ISO/IEC 17020 for inspection and surveillance, and ISO/IEC 17021-1 and ISO/IEC 17065 for system and product certification. This chain ensures the reports and certificates issued are accepted worldwide.

Whether this test can be offered within accredited scope depends on your product and the standard applied; since accreditation is method-based, the scope is confirmed in writing at the quotation stage.

Scope and authorisations

Related Regulations

EU 37/2010 (veterinary drug residue limits)
EU 2023/915 (contaminants in food)
ICH M10 (bioanalytical method validation)

Pages Where This Method Is Used

Analytical Methods — What Does This Group of Methods Do?

The section below describes the field that the LC-MS Analysis test belongs to; the conditions and acceptance criteria of this particular test are given in the sections above. The scope specific to your product is confirmed in writing at the quotation stage.

Analytical method pages are pages about a MEASUREMENT TECHNIQUE rather than about a test. The difference matters: "salt spray testing" is a test and answers one question; "ICP-MS" is a technique and is used in dozens of different tests. Sometimes the user is looking not for the test but for the technique — because the method name is what appears in their specification.

This distinction becomes decisive in choosing a laboratory. When a customer asks for "heavy metal analysis", the real question is by which technique it will be done: XRF is fast and non-destructive but does not distinguish compounds; AAS is economical for a single element; ICP-OES screens multiple elements; ICP-MS sees trace levels. The same sample gives results with different detection limits and different uncertainties across the four techniques.

Method selection is made against three criteria. DETECTION LIMIT: is the concentration sought within the range the method can see? MATRIX COMPATIBILITY: is the sample matrix (plastic, food, soil, metal) one the method can handle, and is pre-treatment required? SPECIFICATION LINK: does the product standard or legislation mandate a particular method? The third often overrides the first two — the specification binds the method.

Method pages build a CHAIN. A technique is linked to the test pages where it is used, to the standards those tests rest on, to the legislation those standards are tied to and ultimately to market access regimes. The example chain in the source document works like this: XRF → metal analysis → RoHS compliance → heavy metal restriction → coating pages. Whichever link the user enters from, they reach the others.

Sample preparation is the invisible half of the result in this family and is a greater source of error than the technique itself. The digestion method, degree of grinding, extraction solvent and dilution ratio change the result markedly. The same sample on the same instrument gives a different result with different preparation; the definition of the method therefore covers preparation too.

Calibration and verification are the third determining component. An instrument is calibrated with certified reference material, the calibration curve is verified periodically and a control sample is run in each batch. Without these steps, a number produced is not traceable even if the instrument is working correctly.

Method groups in this field

Elemental analysis
ICP-OES, ICP-MS, AAS and XRF. They differ in detection limit, matrix tolerance and multi-element capacity.
Chromatography
GC, GC-MS, HPLC, LC-MS/MS and ion chromatography. It separates a mixture into its components and measures each separately.
Spectroscopy
FTIR, Raman, UV-Vis and optical emission. For material identity, functional group identification and alloy composition.
Thermal analysis
DSC, TGA, DMA and dilatometry. Transition temperatures, composition, decomposition and dimensional behaviour.
Microscopy and imaging
Optical microscopy, SEM-EDS, radiography and tomography. Structure, defects and elemental distribution.
Classical (wet) chemistry
Titration, gravimetry and colorimetry. Used as a reference method and in confirming instrumental results.

Commonly confused in this field

XRF is a screening tool; it sees elements and does not distinguish compounds. A decision on a restricted compound requires confirmation by wet chemistry.
The phrase "not detected" is not proof of absence; it is read together with the detection limit of the method.
The specification binds the method. A technically better method is not accepted if the specification calls for another.
Sample preparation is part of the result; a report that does not state the preparation is not reproducible.
Results obtained by different techniques cannot be compared directly; their detection limits and uncertainties differ.
A method page is not a test page; which method applies to which test comes from the product standard.

Which decisions these results support

Matching the method written in the specification to the laboratory's scope
Method selection according to detection limit and matrix compatibility
Confirming an instrumental result with a reference method
Eliminating deviations arising from sample preparation

Related Tests

Frequently Asked Questions About LC-MS Analysis

What is the difference between LC-MS and LC-MS/MS?

LC-MS performs a single mass measurement. LC-MS/MS selects and fragments the precursor ion and monitors product ions; it is far more selective and has a lower limit of quantification in complex matrices.

Why is a volatile buffer needed?

Non-volatile salts accumulate in the ion source, suppressing the signal and contaminating the instrument. Volatile buffers such as formic acid or ammonium acetate are therefore used.