Ptolemy et al. illustrate the long-recognized problem of coeluting drug peaks in cation-exchange amino acid analysis with ninhydrin detection. Such interference is often noted in the urine of patients on antibiotic therapy (ampicillin, amoxicillin), as well as other medications and radiopaque dyes (diatrizoate meglumine). Although anticonvulsants are less often observed, vigabatrin interference in patient urine samples has previously been described by Preece et al. (1) as a large peak eluting near tryptophan (specifically between ammonia and ornithine), undoubtedly representing the same peak as that seen here. Such interference is traditionally evaluated by comparing the ratio of the spectrophotometric absorbances at 570 nm and 440 nm to that from authentic amino acid calibrators. This calculation would have rapidly provided a clue that the peak represented an interferant rather than tryptophan. Additional support could have come by measuring the plasma tryptophan concentration, which is characteristically increased in primary disorders of tryptophan metabolism but, because of rapid renal drug clearance, is normal in cases of drug interference. Hartnup disease, a disorder of neutral amino acid transport, was less likely in this case, both on clinical grounds and because the overall Hartnup excretion pattern (including tryptophan, methionine, lysine, and glycine) was not present.
Interference from exogenous compounds can be overcome, as demonstrated here, by using the more specific approach of mass spectrometry. It is important to note, however, that increases in amino acids can be caused, either directly or indirectly, by a variety of therapies, including valproate (leading to increased glycine), methotrexate (homocysteine), arginine hydrochloride (arginine), and certain preparations of intravenous immunoglobulin (glycine). Analysis by mass spectrometry clearly would not circumvent the interpretive problems introduced by such preparations. Therefore, despite the increasing use of mass spectrometry by clinical laboratories, amino acid results should still be interpreted in the context of clinical, medication, and diet history whenever possible.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication December 16, 2010.
- Accepted for publication December 28, 2010.
- © 2011 The American Association for Clinical Chemistry