Rapid and widespread distribution of doxycycline in rat brain: a mass spectrometric imaging study.

1. The penetration of tetracyclines into the brain has been widely documented. The aim of this work was to develop a matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI) method for the molecular histology of doxycycline (DOX) in the healthy rat brain. 2. The time-dependent distribution was investigated after an i.p. dose of 25 mg/kg at 0, 5, 30, 120, 240, 360 and 480 min postdose. LCMS/MS was used to quantify the drug in plasma and brain homogenates and MALDI MSI was used to determine the distribution of the analyte. 3. Within the first-hour postdose, the drug showed slow accumulation into the plasma and brain tissues. DOX brain concentration gradually increased and reached a peak (Cmax) of 1034.9 ng/mL at 240 min postdose, resulting in a brain plasma ratio of 31%. The images acquired by MSI matched the quantification results and clearly showed drug distribution over the entire rat brain coronal section from 5 min and its slow elimination after 360-min postdose. 4. Our findings confirm that MALDI MSI provides an advanced, label-free and faster alternative technique for xenobiotic distribution such as DOX in tissues, making it an essential drug discovery tool for other possible neuroprotective agents.

Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of tigecycline in rat brain tissues.

Tigecycline (TIG), a derivative of minocycline, is the first in the novel class of glycylcyclines and is currently indicated for the treatment of complicated skin structure and intra-abdominal infections. A selective, accurate and reversed-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of TIG in rat brain tissues. Sample preparation was based on protein precipitation and solid phase extraction using Supel-Select HLB (30 mg/1 mL) cartridges. The samples were separated on a YMC Triart C18 column (150 mm x 3.0 mm. 3.0 µm) using gradient elution. Positive electrospray ionization (ESI+) was used for the detection mechanism with the multiple reaction monitoring (MRM) mode. The method was validated over the concentration range of 150-1200 ng/mL for rat brain tissue. The precision and accuracy for all brain analyses were within the acceptable limit. The mean extraction recovery in rat brain was 83.6%. This validated method was successfully applied to a pharmacokinetic study in female Sprague Dawley rats, which were given a dose of 25 mg/kg TIG intraperitoneally at various time-points. Copyright © 2015 John Wiley & Sons, Ltd.

Polycyclic Aromatic Hydrocarbon Gaseous Emissions from Household Cooking Devices: A Kenyan Case Study.

In developing countries, household energy use is highly variable and complex, yet emissions arising from fuel combustion indoors are typically poorly quantified. Polycyclic aromatic hydrocarbons (PAHs) are emitted during the combustion of organic fuels such as charcoal and biomass. In the present study, multichannel polydimethylsiloxane rubber traps were used for gas-phase PAH sampling and extracted using a low-solvent volume plunger-assisted solvent extraction method. Sixteen US Environmental Protection Agency priority PAHs, primarily in the gas phase, were investigated in indoor air of rural and urban residential homes in coastal Kenya (Mombasa and Taita Taveta Counties) using typical combustion devices of each area. Average gaseous PAH concentrations per household were higher in rural (ranging 0.81-6.09 µg m-3 ) compared to urban (ranging 0-2.59 µg m-3 ) homes, although ambient PAH concentrations were higher in urban environments, likely attributable to traffic contributions. The impact of fuel choice and thereby combustion device on PAH emissions was very clear, with the highest concentrations of PAHs quantified from wood-burning emissions from 3-stone stoves (total PAH averages 46.23 ± 3.24 µg m-3 [n = 6]). Average benzo[a]pyrene equivalent total concentrations were evaluated for the priority PAHs and ranged from not detected to 43.31, 88.38, 309.61, and 453.88 ng m-3 for gas, kerosene, jiko, 3-stone, and improved 3-stone stoves, respectively. Environ Toxicol Chem 2020;39:538-547. © 2019 SETAC.

Development and optimization of a plunger assisted solvent extraction method for polycyclic aromatic hydrocarbons sampled onto multi-channel silicone rubber traps.

A plunger assisted solvent extraction (PASE) method for multi-channel silicone rubber trap samplers was developed and evaluated as an alternative to direct thermal desorption for the monitoring of polycyclic aromatic hydrocarbons (PAHs). The proposed extraction method was simple, fast (a total of 2 min for extraction), and used a small volume of solvent (a total of 2 mL from two sequential 1 mL extractions). The PASE method presented an advantage over thermal desorption in that samples could be re-analyzed, as only a portion of the extract was injected. Additionally, this approach is cost effective and can be applied in laboratories which do not have thermal desorption systems, hence allowing for the more widespread use of the polydimethylsiloxane samplers which can be employed as denuders in the monitoring of gas and particle partitioning of air pollutants. The method was validated over a wide concentration range (0.005-10 ng µL-1) and the limits of detection ranged from 13.6 ng m-3 for naphthalene to 227.1 ng m-3 for indeno[1,2,3-cd]pyrene. Overall extraction efficiencies of the target PAHs were good (from 76% for naphthalene to 99% for phenanthrene) with relative standard deviations below 6%. The PASE method was successfully applied to the analysis of domestic fire air emission samples taken at 10 and 20 min after ignition, using a sampling flow rate of 500 mL min-1 for 10 min in each case. The samples were found to contain primarily naphthalene (maximum concentration of 9.5 µg m-3, 10 min after ignition), as well as fluorene, anthracene, phenanthrene, fluoranthene and pyrene.