A new facile synthesis of d4-pterosin B and d4-bromopterosin, deuterated analogues of ptaquiloside.

Ptaquiloside (Pta) is a potent carcinogen present in bracken fern and in soil matrices, that can potentially leach to the aquatic environment. More recently its presence in the milk of different farm animals has been reported. Pterosin B (Ptb) and bromopterosin (BrPt) represent the most convenient analogues in the detection of ptaquiloside by mass spectrometry. Pterosin sesquiterpenes are also involved in many patented biomedical protocols. In this work we introduce a new and convenient approach to the synthesis in three steps and more than 80% yield of d4-pterosin B (d4-Ptb) and d4-bromopterosin (d4-BrPt), useful as internal standards in the quantification of ptaquiloside.

Reference materials for new psychoactive substances.

Historically, the appearance of new psychoactive materials (and hence the requirement for new reference standards) has been relatively slow. This position has now changed, with 101 new psychoactive substances reported to EMCDDA-Europol since 2006. The newly reported materials, and associated metabolites, require properly certified reference materials to permit reliable identification and quantification. The traditional approach and timescales of reference material production and certification are being increasingly challenged by the appearance of these new substances. Reference material suppliers have to adopt new strategies to meet the needs of laboratories. This situation is particularly challenging for toxicology standards as the metabolism of many of these substances is initially unknown. Reference material production often involves synthesis from first principles. While it is possible to synthesis these materials, there can be significant difficulties, from synthetic complexities through to the need to use controlled materials. These issues are examined through a discussion of the synthesis of cathinones. Use of alternative sources, including pharmaceutical impurity materials or internet sourced products, as starting materials for conversion into appropriately certified reference materials are also discussed. The sudden appearance and sometimes brief lifetime in the market place of many of these novel legal highs or research chemicals present commercial difficulties for reference material producers. The need for collaboration at all levels is highlighted as essential to rapid identification of requirements for new reference materials. National or international commissioning or support may also be required to permit reference material producers to recover their development costs.

Efficacy of indacaterol in the treatment of patients with COPD.

Effective bronchodilation is an important part of the management of patients with chronic obstructive pulmonary disease (COPD) and can improve breathlessness and ability to undertake physical activities. Indacaterol is a new once-daily, long-acting inhaled bronchodilator for COPD. We review here the efficacy of indacaterol as a bronchodilator, including its impact upon symptoms and health status. The evidence reviewed comprises four placebo-controlled clinical studies of indacaterol treatment, three of which included treatment arms with one of the other long-acting inhaled bronchodilators (once-daily tiotropium or twice-daily salmeterol or formoterol), in 4,833 patients with moderate-to-severe COPD. Indacaterol had a bronchodilator effect significantly greater than formoterol and salmeterol, and similar to tiotropium. Its effect on symptoms and health status was similar or significantly greater than the other bronchodilators. The safety profile was similar to placebo. Once-daily indacaterol is an effective and beneficial maintenance bronchodilator treatment for patients with moderate-to-severe COPD.

Stability indicating methods for determination of Donepezil Hydrochloride according to ICH guidelines.

Stability indicating assays for determination of Donepezil Hydrochloride in presence of its oxidative degradate were developed and validated. The first three are spectrophotometric methods depending on using zero order (D(0)), first order (D(1)) and second order (D(2)) spectra. The absorbance was measured at 315 nm for (D(0)) while the amplitude was measured at 332.1nm for (D(1)) and 340 nm for (D(2)) using deionized water as a solvent. Donepezil Hydrochloride (I) can be determined in the presence of up to 70% of its oxidative degradate (II) using (D(0)), 80% using (D(1)) and 90% using (D(2)). The linearity range was found to be 8-56 microg ml(-1) for (D(0)), (D(1)) and (D(2)). These methods were applied for the analysis of I in both powder and tablet form. Also, a spectrofluorimetric method depending on measuring the native fluorescence of I in deionized water using lambda excitation 226 nm and lambda emission 391 nm is suggested. The linearity range was found to be 0.32-3.20 microg ml(-1) using this method, I was determined in the presence of up to 90% of II. The proposed method was applied for the analysis of I in tablet form as well as in human plasma. The last method depends on using TLC separation of I from its oxidative degradate II and I was then determined spectrodensitometrically. The mobile phase was methanol : chloroform : 25% ammonia (16 : 64 : 0.1 by volume). The linearity range was found to be 2-15 microg/spot. This method was applied to the analysis of I in both powder and tablet form using acetonitrile as a solvent.