Methods of Analysis

When MPA was originally approved for use (as mycophenolate mofetil), therapeutic drug monitoring was considered unnecessary. However, recent studies have found wide variations in total drug exposure (as high as 10-fold) following a fixed dose, suggesting that individualized dosing may be of considerable benefit (206,207). A roundtable meeting recently recommended therapeutic drug monitoring based on the interpatient variability and the significant drug interactions associated with combination immunosuppressive therapy (208).

At the present time, fewer than 30 laboratories in the USA measure MPA (1st CAP proficiency survey of 2006). Roughly half the laboratories measure MPA using HPLC, with the majority of remaining laboratories using HPLC-MS methods. Numerous HPLC methods with UV, fluorimetric, and MS detection systems have been described to measure MPA in plasma samples (198,199,209-211). The HPLC methods primarily differ in sample extraction, analytical column, run-time, and lower limit of detection. Free MPA can be measured using HPLC methods after separation of protein-bound MPA by ultrafiltration (185,212). However, free MPA is typically more difficult to measure and does not appear to be superior to total MPA in predicting clinical outcomes in most transplant patients (213).

Automated assays to measure MPA are currently not available in the USA. Several companies are developing product applications for various automated instruments for either serum and/or plasma samples. For instance, Dade-Behring is developing an enhanced turbidimetric inhibition immunoassay to measure MPA for use on Dimension clinical chemistry analyzers (214). Microgenics is developing a CEDIA to measure MPA on Hitachi, Olympus, and Microgenics (MGC 240) clinical chemistry analyzers (215). Lastly, Roche (Roche Diagnostics, Indianapolis, IN, USA) is developing an enzyme receptor assay to measure total MPA and free MPA using the COBAS INTEGRA system (Roche Diagnostics, Indianapolis, IN, USA) (216). At the time of this writing, none of these assays have been submitted to the FDA for review.

Dade-Behring has an EMIT 2000 MPA immunoassay that is widely used outside the USA. The assay can be performed on Dade-Behring Dimension instruments, the Roche COBAS, and Hitachi automated chemistry analyzers. The antibody used in the EMIT assay has cross-reactivity with acyl glucoronide (217) and produces MPA values that are approximately 10-30% higher than those obtained using HPLC (218-221). The bias can be considerably higher in patients with impaired renal function because of accumulation of acyl glucoronide (218,222). The positive bias because of acyl glucoronide cross-reactivity may turn out to be advantageous because metabolite has in vitro anti-IMPDH activity (206,223).

Dealing With Asthma Naturally

Dealing With Asthma Naturally

Do You Suffer From ASTHMA Chronic asthma is a paralyzing, suffocating and socially isolating condition that can cause anxiety that can trigger even more attacks. Before you know it you are caught in a vicious cycle Put an end to the dependence on inhalers, buying expensive prescription drugs and avoidance of allergenic situations and animals. Get control of your life again and Deal With Asthma Naturally

Get My Free Ebook

Post a comment