Lifestyle illicit drug seizures: A routine ESI-LC-MS method for the identification of sildenafil and vardenafil

For street samples suspected of containing the phosphodiesterase-5 inhibitors sildenafil (Viagra(?)) and/or vardenafil (Levitra(?)), including powders or adulterated herbal supplements, a chemical analysis is needed to provide confirmatory identification of these illegally procured substances. Sildenafil and vardenafil are structurally similar and it is difficult to differentiate between them, as previous mass spectrometric studies have shown the two drugs to produce similar fragmentation patterns. The use of tandem mass spectrometry can produce confirmatory data, but the technique requires a high level of technical expertise. We have developed an electrospray ionization-liquid chromatography-mass spectrometry (ESI-LC-MS) method that allows differentiation between these two structurally similar molecules via in-source fragmentation in combination with an ion trap mass spectrometer. A very stable gas phase ion is formed during in-source fragmentation of vardenafil; the combination of the stability of this ion and the longer residence time for the ion in the ion trap results in a very strong signal. This feature results in a method that can provide clear differentiation between sildenafil and vardenafil while at the same time requiring less expertise from the routine analyst to confirm the presence or absence of the two compounds.     

Resolving legal, ethical, and human rights challenges in HIV vaccine research

In the absence of a cure for AIDS, attention has turned to the possibility of developing a preventive vaccine for HIV infection. Yet many scientific, ethical, legal, and economic obstacles remain. At the current rate, the development and production of an effective vaccine could take 15 to 20 years or longer. If tens of millions more HIV infections and deaths are to be avoided in the coming decades, vaccine research needs to be greatly expedited. Furthermore, it must be undertaken ethically, and the products of this research must benefit people in developing countries. This article, an edited and updated version of a paper presented at "Putting Third First," addresses challenges arising in HIV preventive vaccine research in developing countries. It does not address clinical research in developing countries relating to treatments or therapeutic vaccines. Nor does it address legal and ethical issues relating to HIV vaccine research in industrialized countries, although similar issues arise in both contexts. The article concludes that while ethical codes are silent on the obligation to undertake research and development, international law provides strong legal obligations--particularly with regard to industrialized states--that should be invoked to accelerate HIV vaccine development, and distribution.     

Predicting risk for early police arrest

A model designed to predict early arrest is presented. Family process variables were hypothesized to be indirectly related; a childhood measure of an antisocial trait was assumed to be directly related to risk for early onset. Longitudinal data were collected for two cohorts of families living in high-crime areas of a mediumsized metropolitan area. Multiagent/multimethod definitions for both the family process and the antisocial trait concepts defined the latent constructs. Official records of police contacts were collected during the ensuing 5 years. The data for the hazard rates showed that risk for police arrest varied significantly as a function of the child's age. A continuous time regression analysis showed that most of the individual family process constructs and the antisocial trait construct were significantly related to an altered risk for police contacts. A multiple regression analysis showed a similar effect in predicting age at onset. In keeping with the hypotheses in both analyses, when all variables were entered simultaneously the contributions of the family process constructs were nonsignificant; only the contributions for the trait score and social disadvantage remained significant. The more antisocial the child, the greater the risk for early arrest.     

Theoretical Disagreement,Legal Positivism,and Interpretation

Ronald Dworkin famously argued that legal positivism is a defective account of law because it has no account of Theoretical Disagreement. In this article I argue that legal positivism—as advanced by H.L.A. Hart—does not need an account of Theoretical Disagreement. Legal positivism does, however, need a plausible account of interpretation in law. I provide such an account in this article.