UHPLC-MS/MS and UHPLC-HRMS Identification of Zolpidem and Zopiclone Main Urinary Metabolites and Method Development for Their Toxicological Determination.
UHPLC-MS/MS and UHPLC-HRMS identification of zolpidem and zopiclone main urinary metabolites and method development for their toxicological determination.
Drug Test Anal. 2013 Mar 19;
Strano Rossi S, Anzillotti L, Castrignanò E, Frison G, Zancanaro F, Chiarotti M
Zolpidem and zopiclone (Z-compounds) are non-benzodiazepine hypnotics of new generation that can be used in drug-facilitated sexual assault (DFSA). Their determination in biological fluids, mainly urine, is of primary importance; nevertheless, although they are excreted almost entirely as metabolites, available methods deal mainly with the determination of the unmetabolized drug. This paper describes a method for the determination in urine of Z-compounds and their metabolites by ultra-high-pressure liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) and UHPLC coupled with high resolution/high accuracy Orbitrap® mass spectrometry (UHPLC-HRMS). The metabolic profile was studied on real samples collected from subjects in therapy with zolpidem or zopiclone; the main urinary metabolites were identified and their MS behaviour studied by MS/MS and HRMS. Two carboxy- and three hydroxy- metabolites, that could be also detected by gas chromatography/mass spectrometry (GC-MS) as trimethylsylyl derivatives, have been identified for zolpidem. Also, at least one dihydroxilated metabolite was detected. As for zopiclone, the two main metabolites detected were N-demethyl and N-oxide zopiclone. For both substances, the unmetabolized compounds were excreted in low amounts in urine. In consideration of these data, a UHPLC-MS/MS method for the determination of Z-compounds and their main metabolites after isotopic dilution with deuterated analogues of zolpidem and zopiclone and direct injection of urine samples was set up. The proposed UHPLC-MS/MS method appears to be practically applicable for the analysis of urine samples in analytical and forensic toxicology cases, as well as in cases of suspected DFSA. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – drug
Illicit online marketing of locaserin before DEA scheduling.
Obesity (Silver Spring). 2013 Mar 20;
Liang BA, Mackey TK, Archer-Hayes5 AN, Shinn LM
OBJECTIVE.: Anti-obesity drugs have been marketed illicitly by “no prescription” online pharmacies after approval and scheduling by the Drug Enforcement Agency. We wished to assess whether anti-obesity drug Belviq® (locaserin HCl) was available from illicit online vendors before DEA-scheduling when sales are unauthorized. DESIGN AND METHODS.: Online searches of “buy Belviq no prescription” examining first five result pages marketing the drug. Searches were performed from 11/5/2012-12/8/2012, prior to DEA scheduing. RESULTS.: Belviq® is actively marketed by “no prescription” online vendors despite official unavailability and prescription requirements. Approaches included direct-to-consumer advertising using descriptive website URLs; linking to illicit marketers; and directing customers to other weight-loss websites for additional marketing.Finally, large quantities were marketed by business-to-business vendors. CONCLUSION.: Illicit online “no prescription” pharmacies are marketingunauthorized, suspect anti-obesity drugs before DEA scheduling and permitted marketing. Regulators must legally intercede to ensure patient safety and providers must educate patients about online-sourcing risks. HubMed – drug
Conventional chemotherapy or hypomethylating agents for older patients with acute myeloid leukaemia?
Hematol Oncol. 2013 Mar 20;
Ferrara F
Acute myeloid leukaemia (AML) is the second more frequent hematologic malignancy in developed countries and primarily affects older adults with a median age at diagnosis of 69?years. Given the progressive ageing of the general population, the incidence of the disease in elderly people is expected to further increase in the years to come. Along with cytogenetics at diagnosis, age represents the most relevant prognostic factor in AML, in that the outcome steadily declines with increasing age. Reasons for poor prognosis include more frequent unfavourable karyotype and other adverse biologic characteristics, such as high rates of expression of genes drug resistance related and high prevalence of secondary AML. Noticeably, as compared with young adults, poorer results in elderly patients have been reported within any cytogenetic and molecular prognostic subgroup, because of frequent comorbid diseases, which render many patients ineligible to intensive chemotherapy. Therefore, predictive models have been developed with the aim of achieving best therapeutic results avoiding unnecessary toxicity. Following conventional induction therapy, older AML patients have complete remission rates in the range of 45-65%, and fewer than 10% of them survive for a minimum of 5?years. On the other hand, hypomethylating agents, such as azacytidine and decitabine offer the possibility of long-term disease control without necessarily achieving complete remission and can represent a reasonable alternative to intensive chemotherapy. Either intensive chemotherapy or hypomethylating agents have lights and shadows, and the therapeutic selection is often influenced by physician’s and patient’s attitude rather than definite criteria. Research is progress in order to assess predictive biologic factors, which would help clinicians in the selection of patients who can take actual benefit from different therapeutic options. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – drug