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Calibration and Qualification of Chromatography, Mass Spectrometry Instruments

Calibration and Qualification of Chromatography, Mass Spectrometry Instruments

The more complex the instrument, the more important it is to consult with the vendor

Liquid chromatography (LC) and mass spectrometry (MS) instruments require calibration for optimal performance and accurate identification of analytes of interest. In regulated laboratories, these instruments must be calibrated before they go online, after maintenance activities, and after major repairs—a process called qualification. 

Qualification is the documented verification of accuracy, linearity, and other system attributes as intended by the vendor. Qualification requires significant expertise, and with increasing instrument complexity, consulting with the vendor will yield the best results.  

When to calibrate

Ken Moore, PhD, MS curriculum manager at Waters Corporation, provides some insight into how frequently MS systems should be calibrated. He recommends checking or calibrating time-of-flight mass spectrometers daily, whereas quadrupole mass spectrometers will generally be calibrated a few times each year. With consistent laboratory conditions—temperature and humidity—the instrument may require less frequent calibration, “but should be checked regularly,” says Moore. He also cautions that if masses drift from expected values, the instrument should be calibrated. 

Should laboratory staff perform qualification and calibrations?

According to Moore, there are several factors that determine the risks associated with performing qualifications. These include the level of expertise required, laboratory standard operating procedures, how well the laboratory staff has been trained, the need for cleaning, maintenance, or repair procedures prior to calibration, and instrument complexity. “The greater the complexity of the MS instrument (for instance, time-of-flight or advanced MS detection systems), the more important it is to consult with the vendor when it comes to qualification,” he explains. 

There are also factors that can reduce the risk associated with users performing mass tuning and calibrations. Moore recommends periodic cleaning and maintenance, as well as choosing MS systems with automated calibration to reduce variability between users. He also notes that vendor-certified training programs can minimize the risk of improper calibration.

The process and challenges

The calibration process involves infusing several compounds of known mass to construct a calibration curve, which allows the user to maximize the mass accuracy of the instrument. To ensure the instrument achieves the best resolution and highest sensitivity, a tuning procedure is performed. “A typical tuning procedure infuses a known compound and then alters the voltages of the instrument to maximize signal,” explains Moore. 

Calibration and tuning require proper sample preparation and sample dilution. It is also important to work with calibrated pipettes, and ensure standards are stored properly. Any contamination of the solvent, sample, or system can be detrimental to proper calibration and accuracy of results, says Moore. 

To support traceability, Moore recommends documenting evidence of who performed the calibration and when, as well as the compounds used, and methods using compliant-ready software systems. He also notes that calibration standards should be pure and contaminant-free. Laboratories should ensure good laboratory practices and standard operating procedures are in place prior to routine tuning and calibration.

Properly calibrated and tuned instruments are important for accurate, reliable data. Given the complexity of chromatography and mass spectrometry instruments, laboratories should invest in proper training or consult with vendors before undertaking these tasks.