Systems And Methods To Determine Body Drug Concentration From An Oral Fluid

Abstract

Oral fluid for drug testing has several advantages over other specimens: (1) It may be collected noninvasively and under direct supervision; (2) its drug concentration reflects blood-drug concentrations; and (3) it can be processed by conventional drug screening and confirmation methods. This technology provides a system that measures the quantity of a drug (without needing a priori knowledge of the drug) in an oral fluid specimen and translates this level to a blood plasma chug concentration. The method first measures the concentration of a drug in an oral fluid sample. Next, a processor calculates the blood plasma concentration from the measured oral fluid drug concentration. Finally, this blood plasma drug level is utilized to calculate a total body drug concentration.

1 - 20 . (canceled) 
     
     
         21 . A method for determining a donor's adherence to a dosing regimen of a drug, the method comprising the steps of:
 obtaining an oral fluid sample by collecting a sample of oral fluid from the donor,   determining a pH of the oral fluid sample, and readying the oral fluid sample for analysis;   determining a concentration of the drug in the oral fluid sample;   calculating an equivalent expected oral fluid steady state minimum drug concentration (Smin) and an equivalent expected oral fluid steady state maximum drug concentration (Smax) using an expected plasma steady state minimum drug concentration (C ss  min) and an expected plasma steady state maximum drug concentration (C ss  max) according to the following steps:
 if the drug is an acidic drug, determining Smin and Smax using Eq. 5 by inputting C ss  min and C ss  max for P and solving for Smin and Smax (S), respectively:
     S/P =[1+10( pHs-pKa )× fp ]/[1+10( pHp-pKa )× fs ]; and  Eq. 5:
 
 
 if the drug is a basic drug, determining Smin and Smax using Eq. 6 by inputting C ss  min and C ss  max for P and solving for Smin and Smax (S), respectively:
     S/P =[1+10( pKa-pHs )× fp ]/[1+10( pKa-pHp )× fs ];  Eq. 6:
 
 
 wherein:
 pHs is the pH of the oral fluid sample; 
 pH p  is a pH of plasma; 
 pKa is a dissociation constant of the drug; 
 fp is a free fraction of the drug in plasma; and 
 fs is free fraction of the drug in saliva; and 
 
   determining that the donor complies with the dosing regimen of the drug, at steady state, if the measured oral fluid drug concentration is within the range between Smax and Smin, wherein the step of determining the oral fluid drug concentration comprises preparing the sample for toxicological measurement of drug content.   
     
     
         22 . The method of  claim 21  wherein the dosing regimen comprises a plurality of drugs. 
     
     
         23 . The method of  claim 21  wherein the step of obtaining the oral fluid sample comprises collecting a predefined volume of oral fluid from the donor. 
     
     
         24 . The method of  claim 21  wherein the step of obtaining the oral fluid sample further comprises that pH is determined by providing visual indicia of the pH. 
     
     
         25 . The method of  claim 21  wherein the predefined volume of the sample is collected with a simultaneous measurement of the sample pH. 
     
     
         26 . The method of  claim 21  wherein the step of determining concentration of the drug comprises using Liquid Chromatography Tandem Mass Spectrometry. 
     
     
         27 . The method of  claim 21  further comprising evaluating steady state drug levels via oral fluid drug measurements. 
     
     
         28 . The method of  claim 21  further comprising comparing measured oral fluid concentration with an expected oral fluid steady state range based on the prescribed dosing regimen.