LC-MS/MS determination in rabbit plasma of the main photoproduct of RLP068/Cl, a cationic sensitizer proposed for photodynamic therapy (PDT) of microbial infections.

The clinical development of a sensitizer for photodynamic therapy (PDT) requires the structural identification of the photoproducts and their quantification in biological fluids and tissues. We describe the LC-MS identification of the most important photoproducts of a cationic phthalocyanine sensitizer (RLP068/Cl) and a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of the main photoproduct (the cationic phthalimide derivative 3-[(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)oxy]-N,N,N-trimethylbenzenaminium chloride) in rabbit plasma. The tri-deuterated product was used as co-eluting internal standard.

Determination of tetracationic zinc(II) phthalocyanine derivative RLP068 in rabbit serum by liquid chromatography-tandem mass spectrometry.

The development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of the tetracationic zinc(II) phthalocyanine derivative RLP068 in rabbit serum is described. The dodecadeuterated product (RLP068-D12) was used as co-eluting internal standard. RLP068 was isolated from serum samples by solid-phase extraction using weak cationic exchange cartridges (WCX).

Selective ring contraction of 5-spirocyclopropane isoxazolidines mediated by acids.

Thermolysis of 3,4-cis ring-fused 5-spirocyclopropane isoxazolidines 16, 18-21, 33, 34, 38a, and 61, in the presence of a protic acid at 70-110 degrees C, yielded 3,4-cis ring-fused azetidin-2-ones 22-26,41, 42, 46, and 62 with concomitant extrusion of ethylene, in good yields. So far, the collected evidences strongly support a mechanism started by a homolytic cleavage of the protonated N-O bond for the rearrangement of 5-spirocyclopropane isoxazolidines to beta-lactams. Some different competitive pathways can then follow depending on the stability or the stereoelectronic properties of cationic diradical intermediates.