Analytical Considerations

The generally accepted therapeutic range for trough MPA plasma concentrations is 1.0-3.5 mg/L (196,224,225). This range of values can be easily measured by currently available analytical methods with good precision. Concentrations of free MPA are typically 2% of the total MPA level and can be analytically challenging for some of the HPLC-UV methods (226). In these situations, the functional sensitivity of the free MPA assay needs to be carefully validated.

HPLC is the reference method for measuring MPA that other methods are validated against. This is because HPLC is highly specific for parent compound and is free from coadministered drug interferences (200,209-211). As immunoassays to measure MPA become available in the USA, metabolite cross-reactivity and assay bias will have to be taken into account when interpreting MPA concentrations.

6. CONCLUSION

Advances in immunosuppressive therapy are largely responsible for the success and improved outcomes that are now obtained following allogeneic organ transplantation. Today, very few allografts are lost to immune-mediated acute rejection, and there is remarkable improvement in patient and graft survival. A major goal of immuno-suppressive drug therapy is to optimize therapeutic effectiveness while minimizing unwanted adverse effects. Therefore, therapeutic drug monitoring plays a central role because a "one size fits all" approach for immunosuppressive drugs has proved unsuccessful, with optimal drug therapy requiring individualized dosing. Therapeutic monitoring of CsA, tacrolimus, and sirolimus is now considered an integral part of organ transplant programs, and several arguments have been made for monitoring MPA.

Although HPLC is considered the reference method for monitoring immuno-suppressive drugs, the majority of laboratories in the USA are currently using immunoassays. Immunoassays are attractive because they can be automated, have low start-up costs, and do not require highly skilled testing personnel. Their major drawback is metabolite cross-reactivity, which results in varying degrees of positive bias that is unique to each immunoassay. Furthermore, cross-reactivity is not always predictable and can vary depending on post-transplant time and type of organ transplanted. The advantage of HPLC is high specificity and the ability to separate metabolites from parent compound. Drawbacks of HPLC include the need for extensive sample cleanup, long analytical run times, and specialized training. This can be partially overcome by using HPLC with MS detection, which requires less sample preparation and has shorter run times than HPLC with UV detection. Unfortunately, HPLC-MS systems are currently very expensive and require highly trained operating personnel. New HPLC-MS systems with automated sample preparation are emerging that are considerably easier to operate. Given the cost of immunoassay reagents, these newer systems are becoming more cost effective, especially when one considers that HPLC-MS can simultaneously measure multiple immunosuppressive drugs in a single whole blood specimen.

Note: At the time of this book's printing, the Roche total and free MRA assays had just been cleared for use in the United States.

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