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Liposomal amphotericin b interferes with the phosphorus assay on the synchron LX 20 analyzer.

To the Editor:

We report an interference caused by liposomal amphotericin B (AmBisome, Astellas Pharma) in the Synchron LX 20 (Beckman Coulter) phosphorus assay (PHOSm). Two inpatients treated with liposomal amphotericin B for invasive mucormycosis were noted to have significantly increased serum phosphorus concentrations. Serum phosphorus values from patient A ranged from 0.9 mmol/L to 3.1 mmol/L compared with pretreatment values of 0.7 to 0.9 mmol/L (reference interval, 0.8-1.5 mmol/L). Patient B was transferred to our institution after 23 days of amphotericin treatment and had phosphorus values ranging from 1.4 to 3.9 mmol/L. Both patients had slightly increased but stable serum creatinine concentrations (53.0-185.6 [micro]mol/L) and did not exhibit symptoms of hyperphosphatemia. One attending physician suspected a possible interference in the phosphorus assay and contacted the clinical laboratory to initiate investigation.

In contrast to the markedly increased phosphorus values from the Synchron LX20 analyzer, the same serum samples produced phosphorus values within or near the reference interval when tested on other chemistry instruments including the Vitros 950 (Johnson and Johnson) and Advia (Bayer) analyzers (Table 1). Lipemic indices on the Synchron LX20 for samples from patient A were within the reference interval of 0-3 but were increased (7-8) for samples from patient B. Serum triglyceride concentrations for patients A and B were 1.0 and 6.1 mmol/L, respectively. Treatment of samples from both patients with Lipoclear (Iris Sample Processing) to reduce turbidity was associated with a marked decrease in phosphorus results on the Synchron LX20 analyzer (Table 1). According to the product insert, neither Intralipid nor endogenous hyperlipidemia (lipemic index value of 8) interfere with the Beckman PHOSm assay (1). These observations suggest that alterations in sample turbidity related to liposomal amphotericin B rather than increased triglyceride values may have contributed to the false increases of phosphorus values.

A previous study demonstrated that falsely increased phosphorus values may occur in patients with plasma cell dyscrasias and lymphoreticular malignancies associated with abnormal immunoglobulin synthesis (2). Immunofixation studies of patient B revealed an IgG [kappa] paraprotein; however, patient A was negative for a paraprotein. Given the absence of paraprotein in patient A along with the appearance of hyper-phosphatemia beginning at the start of AmBisome therapy, paraprotein interference is a less likely explanation for the hyperphosphatemia in these patients. The manufacturer has also reported positive interference with the Synchron LX20 phosphorus assay for hemolyzed samples and from nafcillin and rifampin (1), factors that were not present in either of the cases we describe. It is theoretically possible that the LX 20 method was reading correctly but the other methods had low recovery. Given the lack of clinical signs or symptoms of hyperphosphatemia in these patients, however, the most likely explanation for the results is interference in the LX 20 phosphorus assay.

The occurrence of severe hyperphosphatemia during treatment with high-dose liposomal amphotericin was reported in a pediatric patient (3), but the possibility of pseudohyperphosphatemia caused by interference of liposomal amphotericin B in the phosphorus assay was not addressed. In this pediatric case, the phosphorus assay was performed on a Synchron LX20 analyzer (Chris Jarvinen, personal communication, January 20, 2006). It may be worthwhile to investigate the potential for AmBisome interference on other analyzers that use a phosphomolybdate ultraviolet assay from other manufacturers. The Johnson and Johnson Vitros analyzer and the Bayer Advia analyzer also use a phosphomolybdate method but use different reaction timing and wavelength measurements than the Synchron LX20, which might minimize susceptibility to AmBisome interference.

AmBisome consists of amphotericin B intercalated into a unilamellar bilayer vesicle consisting of phospholipids and cholesterol and measuring <100 run in diameter. We postulate that biodegradation of the liposomal vehicle may lead to interference due to light scatter or precipitation that affects the absorbance measurements.

In patients receiving liposomal amphotericin B, interference in the Synchron LX20 phosphorus assay may lead to unnecessary treatment with phosphorus-binding agents. These cases illustrate the importance of evaluating the potential role of assay interferences in unexplained abnormal laboratory results. The current observations should also motivate testing of other liposomal-based pharmaceutical agents for similar interference. Liposomal agents currently available include liposomal doxorubicin (Doxil[R], Ortho Biotech Products) and liposomal morphine sulfate (Depodur[R], Endo Pharmaceuticals). Liposomal formulations of other drugs are currently in clinical trials.

DOI: 10.1373/clinchem.2006.078840

References

(1.) PHOSm package insert. Beckman Coulter, Inc. 2005.

(2.) Larner AJ. Pseudohyperphosphatemia. Clin Biochem 1995;28:391-3.

(3.) Jain A, Butani L. Severe hyperphosphatemia resulting from high-dose liposomal amphotericin in a child with leukemia. J Pediatr Hematol Oncol 2003;25:324-6.

Helen L. Bailey [1] Emily M. Chan [2]

[1] Department of Laboratory Medicine University of California San Francisco San Francisco, CA 94110

[2] Clinical Laboratory University of California San Francisco Medical Center San Francisco, CA 94110

* Address correspondence to this author at: The Department of Laboratory Medicine, University of California San Francisco, 505 Parnasus Ave., M-580, San Francisco, CA 94143-0102; fax 415-206-6996; e-mail Helen.bailey@ucsfmedctr.org.
Table 1. Serum phosphorus values obtained on selected chemistry
analyzers.

 Synchron LX 20
 Synchron LX 20, Lipoclear, Advia, Vitros,
 mmol/L mmol/L mmol/L mmol/L

Patient A 3.1 1.6 1.7 1.5
Patient B 3.4 0.9 1 0.8
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Title Annotation:Letters
Author:Bailey, Helen L.; Chan, Emily M.
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Apr 1, 2007
Words:883
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