title: Mathematical equations to calculate true mycophenolic acid concentration in human plasma by using two immunoassays with different cross-reactivities with acyl glucuronide metabolite: comparison of calculated values with values obtained by using an HPLC-UV method.
abstract: BACKGROUND
  Both immunoassays and chromatographic methods are available for therapeutic drug monitoring of mycophenolic acid (MPA). Although chromatographic methods are more precise, immunoassays are widely used in clinical laboratories due to ease of adopting such assays on automated analyzers. We studied the possibility of using mathematical equations to calculate true MPA concentration by accounting for acyl glucuronide cross-reactivities with immunoassays by using two immunoassays with widely different cross-reactivities with the metabolite.
  
  
  METHODS
  We determined MPA concentrations in 20 specimens obtained from transplant recipients using cloned enzyme donor immunoassay (CEDIA) assay and a new particle enhanced turbidimetric inhibition immunoassay (PETINIA) assay. Then we developed mathematical equations to calculate true MPA concentration using values obtained by both immunoassays and reported cross-reactivity of acyl glucuronide with respective immunoassays. Calculated concentrations were compared with values obtained by using a high-performance liquid chromatography combined with ultraviolet detection (HPLC-UV) method.
  
  
  RESULTS
  We obtained good correlation between calculated MPA concentrations and corresponding MPA level obtained by using HPLC-UV method. Using x-axis as the MPA concentrations determined by the HPLC-UV method and y-axis as the calculated MPA level, we observed the following regression equation: y = 1.083x - 0.0995 (r = 0.99, n = 20).
  
  
  CONCLUSIONS
  Mathematical equations can be used to calculate true MPA concentrations using two immunoassays with different cross-reactivities with acyl glucuronide metabolite.
authors.affiliation: Department of Pathology, University of Texas-Houston Medical School, Houston, TX 77030, USA. Amitava.Dasgupta@uth.tmc.edu
authors.forename: Amitava
authors.initials: A
authors.lastname: Dasgupta
authors.forename: Myrtle
authors.initials: M
authors.lastname: Johnson
authors.forename: Gertie
authors.initials: G
authors.lastname: Tso
mesh_terms: D000911:Antibodies, Monoclonal; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003429:Cross Reactions; D016903:Drug Monitoring / Q000379:methods; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D055641:Mathematical Concepts; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000276:immunology; D009391:Nephelometry and Turbidimetry; D012044:Regression Analysis; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D014180:Transplantation
chemical_list: D000911:Antibodies, Monoclonal; D020719:Glucuronides; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid
keywords: CEDIA; HPLC-UV; PETINIA; mathematical equations; mycophenolic acid