Pharmacogenetics (PGx) is becoming an important element of precision and personalized medicine, in particular, for the prediction or explanation of drug metabolism. In the past few years, a number of genotyping assays have been used for PGx testing in clinical laboratories, such as the Roche AmpliChip CYP450 test, Luminex xTAG and AutoGenomics Infiniti assays. Although some common genotypes are identified by these platforms, rare variant genotypes usually cannot be consistently identified. Additional concern is that copy number variants (CNV) are sometimes misinterpreted with some assays, although the newer reagents have improved assay performance. Besides genotype inaccuracies, unfavorable costs have been reported to be associated with these assays [1].  Matrix assisted-laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) has become an alternative method for PGx testing. It is an analytical technology that has been widely used in microbial identification and diagnosis of microbial infections. Recently, this technology has been utilized to analyze single nucleotide variants (SNVs) and CNVs of various genes, for instance, CYP3A4, 3A5, 2C9, 2C19 and 2D6 in amplified DNA with several advantages, including: high throughput, highly automated processes, ease of use for multiplex tests, fast turnaround time and cost effectiveness in terms of labor [2].

Given these advantages, clinical researchers and clinicians have shown tremendous interest in the implementation of this technology for PGx testing in the clinical laboratories, and one might wonder if MALDI-TOF/MS is likely to eliminate conventional genotyping tests in the future. In fact, there are several pitfalls associated with MALDI-TOF/MS that could prevent it from being applied in the clinical laboratories, some of which are listed below:

  1. Inaccurate identification of CNV occurs sometimes.
  2. Salt adduct formation could introduce mass distortion and risk for potential inaccurate identification of the DNA sequence.
  3. Cost is still a significant barrier for some laboratories to adopt MALDI-TOF/MS even though the initial capital investment for MALDI-TOF/MS is lower compared to triple quadrupole mass spectrometry.
  4. No FDA-approved MALDI-TOF/MS platform is currently available for PGx testing; therefore, extensive validation and evaluation are required. This prevents some laboratories, especially hospital based laboratories, from implementing this methodology due to limited resources and expertise to perform the full validation.
  5. Skilled personnel are needed for operating the instrumentation and interpreting the data.

Someone might also wonder if they could use the MALDI-TOF/MS instrumentation in the microbiology laboratory in their facility to do PGx testing, instead of purchasing a brand new instrument dedicated for the testing. For sure, it is feasible; however, it might come with other issues. First of all, agreement from the microbiology laboratory is required before pursuing this path. Higher level of coordination is necessary for smooth implementation of new tests for the existing microbiology instrument. Secondly, cross-contamination might be a problem that prevents its implementation. Additionally, middleware adjustment might be required to connect the instrument to laboratory information system.

The question becomes ‘is it worth implementing this technology and is it likely to eliminate conventional PGx testing?’ By the author’s experience, MALDI-TOF/MS has been of great help to PGx testing. However, further advances and improvement will be necessary before it is widely adopted.



[1] Wu, A. H. (2013) Genotype and phenotype concordance for pharmacogenetic tests through proficiency survey testing. Arch Pathol Lab Med, 137, 1232-1236.

[2] Falzoi, M., Mossa, A., Congeddu, E., Saba, L. and Pani, L. (2010) Multiplex genotyping of CYP3A4, CYP3A5, CYP2C9 and CYP2C19 SNPs using MALDI-TOF mass spectrometry. Pharmacogenomics, 11, 559-571.