Disposition of citalopram in biological specimens from postmortem cases

Citalopram is a bicyclic phthalate compound approved in 1998 by the U.S. Food and Drug Administration for the treatment of depression. It is a highly selective serotonin reuptake inhibitor that appears to have little effect on noradrenaline or dopamine reuptake. Since this drug has only recently been released on the U.S. market, information regarding therapeutic, toxic, and lethal concentrations is sparse. This study reports the detection of citalopram in 22 postmortem cases. Citalopram was identified and quantitated by capillary column gas chromatography with nitrogen phosphorus detection after basic liquid-liquid extraction. Confirmation was achieved by full scan electron impact gas chromatography/mass spectrometry. In the 22 cases studied, heart blood citalopram concentrations ranged from 0.09 to 1.64 mg/L (n = 22, mean +/- SD = 0.51+/-0.43, median = 0.34); femoral blood concentrations ranged from 0.09 to 0.76 mg/L (n = 14, mean +/- SD = 0.34+/-0.23, median = 0.28); and urine concentrations ranged from 0.05 to 276.00 mg/L (n = 13). Liver was analyzed in three cases with citalopram concentrations ranging from 2.22 to 8.08 mg/kg. The average heart blood/femoral blood ratio was 1.26 (range 0.75 to 1.98, n = 14). In each case, the cause of death was not considered to be related to citalopram toxicity. These data may therefore provide a basis for establishing post mortem citalopram concentrations following therapeutic doses.     

Mainstreaming: A case for optimism and cynicism

This paper seeks to evaluate the concept of mainstreaming against a range of feminist critiques of laws and legal systems and to examine the case for the pursuit of feminist politics through mainstreaming strategies. It begins, in section two, by identifying theme sin existing mainstreaming literature, and then in section three considers the potential of mainstreaming to tackle the causes o fine quality. In particular it questions whether mainstreaming can address the patriarchal nature of laws and legal systems and the essentialising tendencies of law, and whether mainstreaming can effectively tackle market-driven inequality. A final section considers the conditions under which feminists might consider engagement with mainstreaming and the limits of such strategies. This revised version was published online in July 2006 with corrections to the Cover Date.     

“A disagreement between allies”: The United Kingdom,the United States,and the Soviet-Japanese territorial dispute, 1945–1956

Russian-Japanese relations are frozen in time by their territorial dispute over the Kuril Islands. In untangling the dispute, scholars have studied the history of Russo-Japanese relations, the USSR’s annexation of the islands in 1945, and the role of the United States as the USSR’s erstwhile wartime ally and Japan’s postwar partner. The United Kingdom, a key player in 1945, has been neglected in these studies. This article analyzes the evolution of the British position on the Soviet-Japanese territorial dispute from 1945 to the establishment of diplomatic relations between the two countries in 1956. The article reveals the marked divergence in this position from that of the United States, proceeding from a disagreement over the interpretation of the 1945 Yalta Agreement. In addition, the article highlights the manipulation of the territorial dispute by the United States to further its own political and security objectives and the British reaction to these maneuvers. Her recent publications includeBack in the USSR: Russia’s Intervention in the Internal Affairs of the Former Soviet Republics and the Implications for United States Policy Toward Russia (with Pamela Jewett) (John F. Kennedy School of Government, 1994).     

Quantitative analysis of multiple illicit drugs in preserved oral fluid by solid-phase extraction and liquid chromatography-tandem mass spectrometry

We present a validated method for the simultaneous analysis of basic drugs which comprises a sample clean-up step, using mixed-mode solid-phase extraction (SPE), followed by LC-MS/MS analysis. Deuterated analogues for all of the analytes of interest were used for quantitation. The applied HPLC gradient ensured the elution of all the drugs examined within 14 min and produced chromatographic peaks of acceptable symmetry. Selectivity of the method was achieved by a combination of retention time, and two precursor-product ion transitions for the non-deuterated analogues. Oral fluid was collected with the Intercept, a FDA approved sampling device that is used on a large scale in the US for workplace drug testing. However, this collection system contains some ingredients (stabilizers and preservatives) that can cause substantial interferences, e.g. ion suppression or enhancement during LC-MS/MS analysis, in the absence of suitable sample pre-treatment. The use of the SPE was demonstrated to be highly effective and led to significant decreases in the interferences. Extraction was found to be both reproducible and efficient with recoveries >76% for all of the analytes. Furthermore, the processed samples were demonstrated to be stable for 48 h, except for cocaine and benzoylecgonine, where a slight negative trend was observed, but did not compromise the quantitation. In all cases the method was linear over the range investigated (2-200 microg/L) with an excellent intra-assay and inter-assay precision (coefficients of variation <10% in most cases) for QC samples spiked at a concentration of 4, 12 and 100 microg/L. Limits of quantitation were estimated to be at 2 microg/L with limits of detection ranging from 0.2 to 0.5 microg/L, which meets the requirements of SAMHSA for oral fluid testing in the workplace. The method was subsequently applied to the analysis of Intercept samples collected at the roadside by the police, and to determine MDMA and MDA levels in oral fluid samples from a controlled study.