Neutral analytes drugs

Analysis of saliva can sometimes replace the analysis of plasma samples since a constant ratio between plasma and saliva concentrations can exist for a number of drugs. The amount of the analyte excreted in saliva depends on both the degree of protonation and the extent of protein binding, implying that neutral analytes that do not tend to bind to proteins can be found in relatively high concentrations in this matrix. 

Strongly and weakly acidic drugs (typically cannabinoids) can be separated by using a C8 column with acetonitrile-phosphate at pH 8 [177] which can, with some limitations, also be used for weakly basic and neutral analytes. 

The reversal of EMO will be observed when two CCS with the same affinity toward analyte enantiomers but with opposite electric charge are used for the enan-tioseparation of a given chiral analyte in the presence of the EOF in the separation system [160]. This is illustrated by Fig. 8 for the neutral chiral drug thalidomide. The origin of the reversal of EMO is that the negatively charged CM-f)-CD decelerates the preferentially bound 5-(-)-thalidomide (Fig. 8a), while the positively charged trimethylammonium salt of P-CD (TMA-P-CD) accelerates it (Fig. 8b). 

Figure 4 presents an example of rapid pKa measurement using a pressure-assisted system in combination with a photodiode array (PDA) detector. The migration time of DMSO (EOF marker) was measured at 220 nm, whereas the migration time of the analyte, naphazoline, was measured at 270 nm. The CE run time as well as data analysis time was drastically reduced. Consequently, this system allows the analysis of more than 96 compounds in one day. The limitation of this method is the application to drugs without UV chromophore at more than 250 nm. In some cases, it was effective to remove DMSO by evaporation under vacuum followed by the addition of methanol or acetonitrile as a neutral marker. 

If the renal clearance of a drug varies with urine flow, as with an extensively reabsorbed neutral drug such as methaqualone, then there may be a random sequence of positive and negative findings during the analysis of consecutive urine samples. In view of these difficulties, the interpretation of analytical data from urine samples alone should not be attempted unless urine is the only fluid available and there is some other information which will allow an estimate of the dose to be made. 

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