Therapeutic drug monitoring for the oral fluids has been widely used over the decade and has become very popular as supportive or alternative matrix for use in forensic studies, including drug testing at workplace. Generally the process requires that the drug enters through saliva by simple diffusion via cell membranes, usually it require the free drug in nonionized and lipid soluble form. The Equilibrium shows the relationship between the saliva’s drug concentration and its level in plasma which is dependent upon the drug binding to the plasma protein, the pKa of the drug and pH of both matrices. The Henderson-Hasselbach equation can help us to better understand the relationship as follows:
Basic drugs: S/P = ([1+ 10(pKd-pHs)]/[1+10(pKd-pHp)])+(fp/fs)
Acidic drugs: S/P = ([1+ 10(pHs-pKa)]/[1+10(pHp-pKa)])+(fp/fs)
Where S = concentration of drug in Saliva, pHs = pH of saliva, P = concentration of drug in plasma, pHp = pH of plasma, pKd = log of ionization constant for basic drugs, pKa = log of ionization constant for acidic drugs, fp = fraction of drug bound to plasma, and fs = fraction of drug bound to saliva.
The pH ranging from 6.2 to 7.0 has been found for unstimulated saliva on the other side the pH can reach up to 8.0 for stimulated oral fluid collections, affecting the detection of specimen concentration of drug. The free portion (unbound) of the drug in the circulating blood is reflected by the saliva at the time of sampling. The reason for the detection of higher concentrations of weekly basic drugs in saliva than in blood is due to the pH of saliva being lower than that of the plasma. As it quite clear that the amount of free drug circulating in the plasma can be related to the saliva drug concentrations, they may also be correlated to pharmacological effects.