Claude Geffroy

Abstract Amino acids, sugars, and nucleobases are considered as the so-called molecular bricks of life, the major subunits of proteins and genetic materials. All three chemical families have been previously detected in meteorites. In dense molecular cloud ice analogs, the formation of a large set of amino acids and sugars (+derivatives) has been observed. In this contribution, we demonstrate that similar ices (H 2 O: 13 CH 3 OH:NH 3 ices, 2:1:1) can also lead to the formation of nucleobases. Using combined UPLC-Orbitrap mass spectrometric and UPLC-SRM-triple quadrupole mass spectrometric analyses, we have unambiguously detected cytosine in these primitive, realistic astrophysical ice analogs. Additionally, a huge variety of nucleobase isomers was observed. These results indicate that all central subunits of biochemical materials may have already been present at early stages of chemical evolution of the protosolar nebula, before accretion toward planetesimals. Consequently, the formation of amino acids, sugars, and nucleobases does not necessarily require secondary alteration processes inside meteoritic parent bodies. They might have been supplied from dense molecular cloud ices toward post-accretional objects, such as nonaqueously modified comets, and subsequently delivered onto the early Earth's surface, potentially triggering the emergence of prebiotic chemistry leading to the first living systems.

Enhancing the selectivity of anticancer drugs currently used in the clinic is of great interest in order to propose more efficient chemotherapies with fewer side effects for patients. In this context, we developed a β-cyclodextrin trimer that binds to circulating albumin to form the corresponding bioconjugate in the bloodstream. This latter can then entrap doxorubicin following its i.v. administration via the formation of a host-guest inclusion complex and deliver the drug in tumors. In this study, we demonstrate that the β-cyclodextrin trimer improves the therapeutic efficacy of doxorubicin for the treatment of a subcutaneous murine Lewis lung carcinoma (LLC) implanted in C57BL/6 mice. This outcome is associated with an increased deposition of doxorubicin in malignant tissues when used in combination with the β-cyclodextrin trimer compared to the administration of the drug alone.

<h3>Background</h3> Pyrazinamide is an antituberculosis agent used in adjunctive treatment of tuberculosis infection in combination with other antituberculosis agents, such as isoniazid, rifampicin and ethambutol. The tablet form is unsuitable for paediatric patients and the pharmacist needs to produce an oral suspension. Data on pyrazinamide stability in an oral suspension are scarce and were produced several decades ago. Thus new stability information is needed. <h3>Purpose</h3> The aim of this study was to determine the stability of 100 mg/mL pyrazinamide oral suspension in commercial compounding excipient Syrspend SF PH4 (FAGRON). <h3>Material and methods</h3> 3 batches of oral suspensions were prepared, using pyrazinamide tablets and Syrspend SF-PH4, packaged in amber vials to protect from light, and stored at room temperature. Several parameters were studied on days 0, 3, 5, 8, 15, 30, 60 and 90 (n=3): physical stability (visual inspection, osmolality measurements) and chemical stability (pH measurement, residual concentrations of pyrazinamide, degradation products identification). Pyrazinamide concentrations were determined using a validated analytical method based on high performance liquid chromatography with UV detection at 280 nm. Chromatographic separation of the analytes was performed with a WATERS C18 ATLANTIS T3 column (150×4.6 mm, 5 μm). The mobile phase was composed of acetonitrile/phosphate buffer at pH 3 (40:60 v/v) and flow rate was adjusted at 1 mL/min. Data were acquired and processed with EMPOWER Software. Microbiological stability was checked according to the test using colony counts on media platings. <h3>Results</h3> No change in physical properties was observed during the study period. Drug concentration remained within ±5% of nominal values over 90 days and no degradation products appeared on the chromatograms. Microbiological media plates remained free from any bacterial or fungal colony. <h3>Conclusion</h3> This study showed that 100 mg/mL pyrazinamide oral suspension in Syrspend SF PH4 was stable for at least 90 days at room temperature, so we determined a shelf life of 90 days for this preparation. Further study, using a mass spectrometer method, will be conducted to confirm this shelf-life. <h3>References and/or acknowledgements</h3> Methodological guidelines for stability studies of hospital pharmaceutical preparations. ICH Guidelines . No conflict of interest