Sedation outcomes for remimazolam, a new benzodiazepine.

Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is expected to be safe and effective for a wide range of patients undergoing intravenous sedation for dental procedures. The aim of this literature review was to evaluate clinical and sedation outcomes for remimazolam, including method of administration, level of sedation at the dose required, and clinical adverse events. An electronic literature search of databases was conducted, and eight articles were selected for inclusion in this review. Onset time from drug administration to optimal sedation level was faster for remimazolam (around 1.5-6.4 min) than for midazolam. Recovery time was significantly shorter for remimazolam than for midazolam and propofol. A study comparing various doses of remimazolam with midazolam found no significant difference in safety. Comparison of a remimazolam group with a propofol group showed that incidences of hypotension (13.0% vs 42.9%, respectively) and respiratory depression (1.1% vs 6.9%, respectively) were significantly lower for remimazolam. Remimazolam appears to be an ideal sedative.

Determination of niacin and its metabolites using supercritical fluid chromatography coupled to tandem mass spectrometry.

Niacin, a water-soluble vitamin belonging to the vitamin B group, has been known to cause various problems in the human body when deficient. The vitamin is derived from the diet and afterwards, niacin and its metabolites are secreted in blood or urine. It can be analyzed using liquid chromatography (LC) coupled to mass spectrometry, but niacin and its metabolites are very polar compounds. Recently, supercritical fluid chromatography (SFC) is gaining attention for polar compound analysis. To our best knowledge, the report on the analysis of endogenous-very hydrophilic metabolites in biofluids by SFC has not been found. In this study, we investigated whether the separation of hydrophilic metabolites in biofluids is achievable by SFC. In addition, we also examined the applicability of SFC coupled to MS in extrapolating unknown metabolites by means of spectra information. As a result, an analysis method to quantify the target compounds using SFC/MS/MS was constructed for niacin and its metabolites. Additional putative metabolites from niacin were also identified using the MS fragmentation spectra in plasma and urine. Consequently, the method using SFC/MS/MS allowed for the analysis of polar compounds with low log P ranging from -3.7 to 0.29. This study is the first report of the separation of niacin and its seven metabolites in human urine and these results showed that SFC-MS/MS can be an alternative technique for hydrophilic metabolite analysis.

Simultaneous analysis for water- and fat-soluble vitamins by a novel single chromatography technique unifying supercritical fluid chromatography and liquid chromatography.

Chromatography techniques usually use a single state in the mobile phase, such as liquid, gas, or supercritical fluid. Chromatographers manage one of these techniques for their purpose but are sometimes required to use multiple methods, or even worse, multiple techniques when the target compounds have a wide range of chemical properties. To overcome this challenge, we developed a single method covering a diverse compound range by means of a "unified" chromatography which completely bridges supercritical fluid chromatography and liquid chromatography. In our method, the phase state was continuously changed in the following order; supercritical, subcritical and liquid. Moreover, the gradient of the mobile phase starting at almost 100% CO2 was replaced with 100% methanol at the end completely. As a result, this approach achieved further extension of the polarity range of the mobile phase in a single run, and successfully enabled the simultaneous analysis of fat- and water-soluble vitamins with a wide logP range of -2.11 to 10.12. Furthermore, the 17 vitamins were exceptionally separated in 4min. Our results indicated that the use of dense CO2 and the replacement of CO2 by methanol are practical approaches in unified chromatography covering diverse compounds. Additionally, this is a first report to apply the novel approach to unified chromatography, and can open another door for diverse compound analysis in a single chromatographic technique with single injection, single column and single system.

Supercritical fluid chromatography/mass spectrometry in metabolite analysis.

Supercritical fluid chromatography (SFC) owes many of its advantages to the properties of supercritical CO2, which possesses benefits as mobile phase. SFC has recently gained attention as a separation technique because it can be utilized for not only non-polar but also polar compound analysis. In addition, MS is widely adopted for SFC, and the options for MS are equivalent to liquid chromatography. Sensitive and selective detection is crucial in metabolite analysis. The SFC/MS system can be an alternative approach to liquid chromatography, as can metabolite analysis using packed-column SFC in biosamples. In this review we cover the fundamentals of SFC in combination with MS, and discuss the results of metabolite analysis using SFC/MS.

Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase ß and regulates complex V activity.

Adenosine triphosphate (ATP) synthase ß, the catalytic subunit of mitochondrial complex V, synthesizes ATP. We show that ATP synthase ß is deacetylated by a human nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, sirtuin 3, and its Drosophila melanogaster homologue, dSirt2. dsirt2 mutant flies displayed increased acetylation of specific Lys residues in ATP synthase ß and decreased complex V activity. Overexpression of dSirt2 increased complex V activity. Substitution of Lys 259 and Lys 480 with Arg in human ATP synthase ß, mimicking deacetylation, increased complex V activity, whereas substitution with Gln, mimicking acetylation, decreased activity. Mass spectrometry and proteomic experiments from wild-type and dsirt2 mitochondria identified the Drosophila mitochondrial acetylome and revealed dSirt2 as an important regulator of mitochondrial energy metabolism. Additionally, we unravel a ceramide-NAD(+)-sirtuin axis wherein increased ceramide, a sphingolipid known to induce stress responses, resulted in depletion of NAD(+) and consequent decrease in sirtuin activity. These results provide insight into sirtuin-mediated regulation of complex V and reveal a novel link between ceramide and Drosophila acetylome.

Simultaneous and rapid analysis of bile acids including conjugates by supercritical fluid chromatography coupled to tandem mass spectrometry.

A number of analysis methods for bile acids using LC-MS and GC-MS have been reported. However, there is no reported method for the simultaneous analysis of bile acids using supercritical fluid chromatography (SFC). In this study, we have successfully developed a rapid method using SFC coupled to electrospray ionization tandem mass spectrometry (ESI-MS/MS) for comprehensive bile acid profiling. 25 bile acids including glycine and taurine conjugates were analyzed simultaneously within 13min. The method was applied to rat serum samples, 24 of the bile acids were quantified without any solid-phase extraction and complicated sample preparation. This study not only reports simultaneous analysis of bile acids including conjugates but also indicates the method is applicable to a biological sample. This is the first report on the simultaneous analysis of bile acids using SFC/MS. The developed method will be an alternative to existing analysis methodology for studies on the bile acid metabolism in the medical and pharmaceutical fields.