High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002–2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H]+ and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H]- ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MSn analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well

The forgotten ocean: Why COP26 must call for vastly greater ambition and urgency to address ocean change

1. Of all the interconnected threats facing the planet, the top two are the climate and the biodiversity crises. Neither problem will be solved if we ignore the ocean. To turn the tide in favour of humanity and a habitable planet, we need to recognize and better value the fundamental role that the ocean plays in the earth system, and prioritize the urgent action needed to heal and protect the ocean at the ‘Earthscape’ level – the planetary scale at which processes to support life operate. 2. The countries gathering at COP26 have unparalleled political capacity and leadership to make this happen. COP26 could be the turning point, but there must be commitment to united action for the ocean, as well as planning to meet those commitments, based on science-led solutions that address the interconnectivity of the ocean, climate, and biodiversity. 3. Key ways in which the ocean both contributes to and acts as the major buffer for climate change are summarized, focusing on temperature, but not forgetting the role of storing carbon. It is noted with ‘high confidence’ that the ocean has stored 91% of the excess heat from global warming, with land, melting ice, and the atmosphere only taking up approximately 5, 3, and 1%, respectively. 4. We also highlight the impact of the recent large release of heat from the ocean to the atmosphere during the 2015–2016 El Niño. We then present six science-based policy actions that form a recovery stimulus package for people, climate, nature, and the planet. Our proposals highlight what is needed to view, value, and treat the planet, including the ocean, for the benefit and future of all life.</p

The forgotten ocean: Why COP26 must call for vastly greater ambition and urgency to address ocean change

1.Of all the interconnected threats facing the planet, the top two are the climate and the biodiversity crises. Neither problem will be solved if we ignore the ocean. To turn the tide in favour of humanity and a habitable planet, we need to recognize and better value the fundamental role that the ocean plays in the earth system, and prioritize the urgent action needed to heal and protect the ocean at the ‘Earthscape’ level – the planetary scale at which processes to support life operate. 2.The countries gathering at COP26 have unparalleled political capacity and leadership to make this happen. COP26 could be the turning point, but there must be commitment to united action for the ocean, as well as planning to meet those commitments, based on science-led solutions that address the interconnectivity of the ocean, climate, and biodiversity. 3.Key ways in which the ocean both contributes to and acts as the major buffer for climate change are summarized, focusing on temperature, but not forgetting the role of storing carbon. It is noted with ‘high confidence’ that the ocean has stored 91% of the excess heat from global warming, with land, melting ice, and the atmosphere only taking up approximately 5, 3, and 1%, respectively. 4.We also highlight the impact of the recent large release of heat from the ocean to the atmosphere during the 2015–2016 El Niño. We then present six science-based policy actions that form a recovery stimulus package for people, climate, nature, and the planet. Our proposals highlight what is needed to view, value, and treat the planet, including the ocean, for the benefit and future of all life

A global biogeographic classification of the mesopelagic zone

We have developed a global biogeographic classification of the mesopelagic zone to reflect the regional scales over which the ocean interior varies in terms of biodiversity and function. An integrated approach was necessary, as global gaps in information and variable sampling methods preclude strictly statistical approaches. A panel combining expertise in oceanography, geospatial mapping, and deep-sea biology convened to collate expert opinion on the distributional patterns of pelagic fauna relative to environmental proxies (temperature, salinity, and dissolved oxygen at mesopelagic depths). An iterative Delphi Method integrating additional biological and physical data was used to classify biogeographic ecoregions and to identify the location of ecoregion boundaries or inter-regions gradients. We define 33 global mesopelagic ecoregions. Of these, 20 are oceanic while 13 are ‘distant neritic.’ While each is driven by a complex of controlling factors, the putative primary driver of each ecoregion was identified. While work remains to be done to produce a comprehensive and robust mesopelagic biogeography (i.e., reflecting temporal variation), we believe that the classification set forth in this study will prove to be a useful and timely input to policy planning and management for conservation of deep-pelagic marine resources. In particular, it gives an indication of the spatial scale at which faunal communities are expected to be broadly similar in composition, and hence can inform application of ecosystem-based management approaches, marine spatial planning and the distribution and spacing of networks of representative protected areas