Multiplex Analysis of 230 Medications and 30 Illicit Compounds in Dried Blood Spots and Urine.

Drugs of abuse and medication reconciliation testing can benefit from analysis methods capable of detecting a broader range of drug classes and analytes. Mass spectrometry analysis of a wide variety of commonly prescribed medications and over-the-counter drugs per sample also allows for application of a drug-drug interaction (DDI) algorithm to detect adverse drug reactions. In order to prevent adulteration of commonly collected clinical samples such as urine, dried blood spots (DBS) present a reliable alternative. A novel method is described for qualitative and quantitative multiplex analysis of 230 parent drugs, 30 illicit drugs and 43 confirmatory metabolites by HPLC-MS-MS This method is applicable to DBS specimens collected by volumetric absorptive microsamplers and confirmable in urine specimens. A patient cohort (n = 67) providing simultaneous urine specimens and DBS resulted in 100% positive predictive values of medications or illicits confirmed by detection of a parent drug and/or its metabolite during routine medication adherence analysis. An additional 5,508 DBS specimens screened (n = 5,575) showed 5,428 (97%) with an inconsistent positive compared to the provided medication list (including caffeine, cotinine or ethanol metabolites), 29 (0.5%) with no medication list and no unexpected positive results (consistent negative) and 22 (0.4%) showed all positive results matching the provided medication list (consistent positive). A DDI algorithm applied to all positive results revealed 17% with serious and 56% with moderate DDI warnings. Comprehensive DBS analysis proves a reliable alternative to urine drug testing for extended medication reconciliation, with the added advantage of detecting DDIs.

Translocation of single-stranded DNA through the α-hemolysin protein nanopore in acidic solutions.

The effect of acidic pH on the translocation of single-stranded DNA through the α-hemolysin pore is investigated. Two significantly different types of events, i.e. deep blockades and shallow blockades, are observed at low pH. The residence times of the shallow blockades are not significantly different from those of the DNA translocation events obtained at or near physiological pH, whereas the deep blockades have much larger residence times and blockage amplitudes. With a decrease in the pH of the electrolyte solution, the percentage of the deep blockades in the total events increases. Furthermore, the mean residence time of these long-lived events is dependent on the length of DNA, and also varies with the nucleotide base, suggesting that they are appropriate for use in DNA analysis. In addition to being used as an effective approach to affect DNA translocation in the nanopore, manipulation of the pH of the electrolyte solution provides a potential means to greatly enhance the sensitivity of nanopore stochastic sensing.