Ghost Peaks in HPLC and LC-MS: Solvent Blanks and Contamination

An unexpected peak does not identify its source

An unexpected sample peak is not sufficient evidence that a solvent is unsuitable. Carryover, vials or caps, bottles, mobile-phase additives, columns and accumulated system contaminants may also require investigation. Start by recording the conditions under which the signal repeats.

Document the method, gradient, wavelength or MS settings and recent maintenance before replacing a solvent. Changing several variables together makes it harder to establish which change affected the result.

What can blank checks distinguish?

A solvent blank evaluates background without the sample. Where appropriate, running a gradient without an injection can help distinguish injector-related contributions from the mobile-phase or pump side. The Waters example concerns particular instruments; its menu instructions should not be transferred directly to another system.

• Record whether the signal decreases after a sample and whether it recurs in blanks.
• Keep water, solvent, additive, vial and bottle lots traceable.
• Compare new lots against the laboratory’s blank and system-suitability criteria.

Do not assign every solvent the same role

Review critical specifications when selecting HPLC, UHPLC-MS or LC-MS water, methanol or acetonitrile; a grade name alone does not establish equivalence. Ethanol, 2-propanol and DMSO should only be considered for roles permitted by the method and instrument. Not every solvent is suitable as a mobile phase or wash solvent in every analysis.

Information for a sourcing enquiry

• Specify the product code, required grade, instrument and detector.
• Review the relevant sample and blank conditions with your technical team.
• Request the current TDS, an SDS in the required language and a lot CoA where needed.
• Complete your laboratory’s suitability assessment before accepting a replacement product.