Introduction

The Company’s AUF technology will allow the preparation of ultra-filtrates of serum and plasma samples, for measurement of free therapeutic drugs and hormones to be done quickly on an automated system.

Why is Measurement of Free and Total Drugs important?

Serum or plasma is used to determine the concentration of therapeutic drugs in a patient’s blood.  Tests for hormone and therapeutic drug levels are usually performed using immunoassays performed on laboratory immunoanalyzers.  With the exception given below, immunoassays are incapable of discriminating the free drugs/hormones from the bound drugs/hormones, and measure total drugs/hormones.  Dilantin is a common drug use to treat epilepsy, and will be used as an example.  About 90-95 % of Dilantin binds to proteins in the blood system, the protein rendering most of the drugs inactive.  There are a variety of conditions (e.g., pregnancy and certain diseases) that changes the protein concentration in a patient’s blood, whereby the total drug concentration can change dramatically.  However, the change in free drug concentration could be very small.  Some drugs have a narrow therapeutic range.  In other words, the drug is ineffective if it is below the lower limit of the therapeutic range, and toxic if it is above the upper limit of the therapeutic range.  In a patient with low total protein, the total drug concentration may be low due to the low total protein, but the patient’s free drug concentration could be above the upper limit of the therapeutic range and therefore in the toxic level.  In order to measure the free drug/hormone, an additional manual step of separating the protein-free fraction from the sample must be taken. This is done by a process that incorporates either equilibrium dialysis or centrifugation.  About eighteen hours are required to perform equilibrium dialysis, and thirty minutes are required for centrifugation to separate protein-free serum/plasma, referred to as a serum/plasma ultra-filtrate.  

In 1976, the first commercial immunoassay designed specifically to measure free thyroid hormone became available. The availability of free thyroid hormone measurement revolutionized the way thyroid disorders (a common medical disorder) are diagnosed and treated.  Today it is difficult to find a laboratory that measures total thyroid hormone, since measurement of free thyroid hormone has become standard practice. To date, very few new assays are available for measuring free drugs or free hormones.  Development of immunoassays for free therapeutic drugs and free hormones are difficult and expensive. The ChroMedX alternative is to rapidly modify the sample in a disposable cartridge that can be presented to the existing immunoanalyzer.

Unless the free drug is measured, it is more likely that a patient will be misdiagnosed if the total drug concentration is used, but free drug measurement is usually not available due to cost and long result turnaround time.  The ChroMedX AUF (Automated Ultra-filtration) disposable cartridge provides a rapid inexpensive way of preparing samples for analysis of free hormones and therapeutic drugs.  The cartridges can be designed to be part of a fully automated immunoassay system, a stand-alone processing workstation or as manual sample preparation kits.