Simultaneous Determination of 11 Related Impurities in Propofol by Gas Chromatography/tandem Mass Spectrometry Coupled With Pulsed Splitless Injection Technique.

Simultaneous determination of 11 related impurities in propofol by gas chromatography/tandem mass spectrometry coupled with pulsed splitless injection technique.

J Sep Sci. 2013 Jun; 36(12): 1959-66
Peng M, Le J, Yang Y

A variety of related impurities, including starting materials, process impurities, and degradation products, can be detected in propofol. In this article, a sensitive and selective GC-MS/MS method using pulsed splitless injection technique for the determination of 11 main related impurities in propofol in one chromatogram is investigated. This method is extensively validated for its linearity, recovery, precision, LOD, and LOQ, and is able to detect trace-level related impurities (LOD = 0.2-5.6 ?g/g) in propofol bulk drug. Stressed tests proposed that oxidative degradation, photolytic degradation, and heat are the main causes for the formation of degradation products in propofol. HubMed – drug

Assessing the subjective and physiological effects of intranasally administered crushed extended-release morphine formulations with and without a sequestered naltrexone core in recreational opioid users.

Pain Res Manag. 2013 Jul-Aug; 18(4): e55-62
Setnik B, Goli V, Levy-Cooperman N, Mills C, Shram M, Smith I

To evaluate the pharmacodynamic (PD) effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN) capsules compared with controlled-release morphine sulfate (MS) and placebo when crushed and administered intranasally. The present study was a randomized, double-blinded, placebo-controlled, single-dose (30 mg), three-way crossover study in healthy, nondependent recreational opioid users. PD measures included assessment of subjective drug effects using visual analogue scales (VAS) ranging from 0 to 100 and assessments of pupil diameter. Blood samples were collected for pharmacokinetic analyses. Both MS and MSN showed significantly higher PD values compared with placebo. MSN showed significantly lower scores for drug liking and high VAS scores on both mean peak effect (Emax) (69.6 and 55.2, respectively) and in area under the effect curve over 2 h (86.3 and 66.7, respectively) following dosing compared with MS (Emax 87.6 and 86.6, respectively; area under the curve over 2 h 120.6 and 132.9, respectively; P<0.001). MSN showed significantly lower Emax for all other positive subjective effects (good drug effects, overall drug liking, and take drug again VAS scores) compared with MS (P<0.001). Peak minimum pupil diameter was significantly larger for MSN than MS (P=0.002). Mean peak plasma concentration (Cmax) and median time to Cmax for morphine following administration of MSN and MS were similar (27.3 ng?mL and 0.57 h versus 27.7 ng?mL and 0.6 h, respectively). Naltrexone mean Cmax was 1497 pg?mL after MSN and median time to Cmax was 0.55 h. When crushed and administered intranasally, MSN was associated with significantly lower ratings of drug liking and other positive subjective effects compared with MS. HubMed – drug

Optimal oxygen titration in patients with chronic obstructive pulmonary disease: A role for automated oxygen delivery?

Can Respir J. 2013 Jul-Aug; 20(4): 259-61
Lellouche F, Lipes J, L’her E

Oxygen therapy can be life-saving for patients with chronic obstructive pulmonary disease (COPD) and is the backbone of any acute COPD treatment strategy. Although largely considered to be a benign drug, many publications have highlighted the need to accurately adjust oxygen delivery to avoid both hypoxemia and the problem of hyperoxia-induced hypercapnia. Recent clinical data have shown that the deleterious effects of excess oxygen treatment can not only alter carbon dioxide levels (which has been known for more than 60 years) but can also lead to an increase in mortality. Nevertheless, despite the extensive literature, the risks associated with hyperoxia are often overlooked and published clinical recommendations are largely ignored. This failure in knowledge translation has become increasingly important not only because of the desire to reduce medical error, but in a society with limited health care resources, the economic burden of COPD is such that it cannot afford to make preventable medical mistakes. Recently, novel devices have been developed to automatically adjust oxygen flow rates to maintain stable oxygen saturations. These closed-loop oxygen delivery systems have the potential to reduce medical error, improve morbidity and mortality, and reduce health care costs. Preliminary data in this field are promising and will require a significant amount of research in the coming years to determine the precise indications for these systems. The importance of appropriate oxygen dosing and the current literature regarding novel oxygen delivery systems are reviewed. HubMed – drug