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Ibuprofen and naproxen interference on the measurment of mycophenolic acid in human plasma by HPLC-UV method

BACKGROUND-AIM: Mycophenolic acid is an immunosuppressant drug which is usually used for the prevention of organ rejection after transplantation. The aim of our study was to determine the effect of widely used anti-inflammatory agents, ibuprofen and naproxen, as possible interfering compounds on the measurement of mycophenolic acid (MPA) by high-performance liquid chromatography method with UV detection (HPLC-UV) using the commercially available kit (Recipe, Germany). METHODS: Samples of 4 healthy volunteers, of which 2 were taking ibuprofen and 2 naproxen, have been measured when a concentration of the drug in the plasma was the highest (1 and 3 hours post-dose, respectively). Plasma samples have been analyzed by the HPLC-UV method accredited according to ISO 15189, afterward, combined with patient and 2 external quality control samples. RESULTS: When analyzing samples containing ibuprofen no interference has been observed. Samples containing naproxen had the internal standard (IS) peak area 5-6 time greater than other samples. Consequently, MPA concentration, decreased from 5, 9 mg/L to 2, 6 mg/L and from 7, 6 mg/L to 3, 0 mg/L in two external quality control samples. The same result has been observed with the patient sample - the concentration of MPA decreased from 1, 5 mg/L to 0, 8 mg/L. CONCLUSION: Presence of naproxen in samples, caused elevation of IS peak area and consequently false-low MPA concentrations while ibuprofen showed no interference. Possible co-administered medicatons (naproxen) in organ –transplant patients could cause interferences in MPA measurements pointing out the importance of standardization of pre-analytical proccess including patients prepartion who shouldn’t take naproxen at least 24 hours before MPA measurement. According to some studies, naproxen has retention time similar to MPAs. So, it’s possible that manufacturer uses naproxen as IS, causing in that way a significant interference.

Ibuprophen, Naproxen, HPLC, Mycophenolic acid

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