Identification of photochemical oxidation products of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin by on-line high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

Jones, Russell M.; Wang, Q.; Lamb, John H.; Djelal, Birgul D.; Bonnett, Raymond; Lim, Chang Kee

doi:10.1016/0021-9673(95)00426-2

Cited by 26 publications

(24 citation statements)

References 4 publications

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“…5(iv)), and could result from the dehydrogenation of m-THPC. 9 The decrease in signal cluster intensity at m/z 744 confirmed our hypothesis that this signal cluster belongs to the photoproduct with a Qband at 620 nm.…”

Section: Maldi Experiments At 355 Nmsupporting

confidence: 77%

“…Chlorin N-oxide and hydroxychlorin type photoproducts arise from the addition of one oxygen atom to the m-THPC molecule. This was proposed in a study by Jones et al 9 to explain the nature of photoproducts formed under mild photooxidation conditions and assessed by HPLC electrospray ionization tandem mass spectrometry (HPLC/ESI-MS). Of two possible types of photoproducts, namely, m-THPC N-oxide and hydroxy-m-THPC, only the latter is plausible, since chlorin N-oxide products are unusual and not known in the tetraphenylchlorin series.…”

Section: Maldi Experiments At 355 Nmmentioning

confidence: 96%

“…Of two possible types of photoproducts, namely, m-THPC N-oxide and hydroxy-m-THPC, only the latter is plausible, since chlorin N-oxide products are unusual and not known in the tetraphenylchlorin series. 9 Taking this fact into account, we propose that the phototransformation of the m-THPC molecule, under our experimental conditions, yields the photoproduct formation with the hydroxyl group attached to the pyrrole ring (either in the unsaturated or reduced position) or to the hydroxyphenyl ring. Also, photoproducts as the monohydroxylated chlorin N-oxide and/or monohydroxylated epoxide are feasible.…”

Section: Maldi Experiments At 355 Nmmentioning

confidence: 97%

“…This process, usually called 'photobleaching', involves a decrease in absorbance for certain spectral bands, variations of the fluorescence intensity or the formation of new absorption and emission bands. 7 The m-THPC photodegradation has been observed in aqueous 8 and organic solutions, 9 in vitro, 10 in vivo in tumor-bearing mice 11 and in clinical practice. 12 Studyies of the photobleaching reaction are particularly important for two reasons: (1) Identification of photobleaching products, which can be photodynamically active, thus opening the possibility for 'extended' photodynamic therapy; (2) Measurement of the photochemical reactions that reflect the potential therapeutic effect and thus help to match the light dose.…”

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confidence: 99%

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Matrix-assisted laser desorption/Ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry: a method to characterize temoporpfin photoproducts

Angotti¹,

Maunit²,

Müller³

et al. 1999

Rapid Commun. Mass Spectrom.

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Photodynamic therapy (PDT) is a new rapidly developing method for cancer treatment, which is based on the systemic administration of a tumor-localizing photosensitizer (PS), followed by irradiation of the tumor with visible spectrally adapted light.1-3 The photochemical interaction of the PS, light and molecular oxygen results in the formation of singlet oxygen ( 1 O 2 ) and other reactive oxygen species (ROS), which are believed to be toxic species responsible for induction of tumor necrosis.2,3 5,10,15,20-m-(Tetrahydroxyphenyl)chlorin (m-THPC), one of the second generation photosensitizers, 4 has recently been proposed as a new sensitizer for future use in the PDT of cancer.5,6 m-THPC is a single compound, derived from 5,10,15,20-meso-(tetrahydroxyphenyl)porphyrin (m-THPP), 4 with a maximum absorption in the red region of visible light (! max 652 nm). The latter property favors deeper light penetration into tissue and allows the method to achieve 6-10 mm depth of necrosis in tumor-bearing mice. As is the case for the majority of photosensitive drugs, m-THPC is degraded upon light illumination. This process, usually called 'photobleaching', involves a decrease in absorbance for certain spectral bands, variations of the fluorescence intensity or the formation of new absorption and emission bands.7 The m-THPC photodegradation has been observed in aqueous 8 and organic solutions, 9 in vitro, 10 in vivo in tumor-bearing mice 11 and in clinical practice. 12Studyies of the photobleaching reaction are particularly important for two reasons: (1) Identification of photobleaching products, which can be photodynamically active, thus opening the possibility for 'extended' photodynamic therapy; (2) Measurement of the photochemical reactions that reflect the potential therapeutic effect and thus help to match the light dose. This paper describes the first results concerning the application of matrix-assisted laser desorption/ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICRMS) for the analysis of the parent m-THPC molecule and the products of photochemical m-THPC oxidation. We have studied the formation of photoproducts in organic solvents as a result of two consecutive irradiations separated by a dark storage period. The kinetics of photoproduct formation, assessed by MALDI, have been compared with that obtained by spectroscopic measurements. EXPERIMENTALReagents and standard solutions m-THPC (Fig. 1) was kindly provided by Scotia Pharmaceuticals Ltd. (Guildford, UK) as crystalline powder (specification: content of m-THPC: 98.4% w/w; water content: 0.20% w/w; residual solvents: ethanol 0.18% w/w; content of impurities: m-THPP 0.7% w/w). Unless otherwise indicated, the photosensitizer was dissolved in methanol or in ethanol (Prolabo SA, Fontenay sous bois, France), which had been distilled beforehand twice under an inert atmosphere. IlluminationIllumination was performed by exposing 3.5 mL of 7 mg/mL (10 À5 mol/L) of m-THPC in ethanol or methanol in a quartz cuvette (pathlength 1 c...

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Section: Maldi Experiments At 355 Nmsupporting

confidence: 77%

Section: Maldi Experiments At 355 Nmmentioning

confidence: 96%

Section: Maldi Experiments At 355 Nmmentioning

confidence: 97%

mentioning

confidence: 99%

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Matrix-assisted laser desorption/Ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry: a method to characterize temoporpfin photoproducts

Angotti¹,

Maunit²,

Müller³

et al. 1999

Rapid Commun. Mass Spectrom.

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show abstract

“…9), rather than at a double bond of a pyrrole or phenyl ring. 83) Peaks 1 and 2 are therefore degradation products caused by the oxidation of m-THPC.…”

Section: Fig 5 Hplc-esi-ms Separation Of Tamoxifen and Metabolites mentioning

confidence: 99%

Current Developments in LC-MS for Pharmaceutical Analysis

Lim

Lord

2002

Biological & Pharmaceutical Bulletin

151

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Liquid chromatography-mass spectrometry (LC-MS) is an analytical technique that couples high resolution chromatographic separation with sensitive and specific mass spectrometric detection. This includes high performance liquid chromatography (HPLC)-MS, capillary electrophoresis (CE)-MS and more recently capillary electrochromatography (CEC)-MS. The technique is still fast developing, particularly in the mass spectrometry area, with vastly improved sensitivity and resolution. It is probably the most powerful technique currently available for pharmaceutical analysis.This review is intended as a discussion on the current developments of LC-MS in pharmaceutical analysis rather than a review of literature alone. Various LC-MS techniques will be described briefly and the advantages and disadvantages of each will be discussed. DEVELOPMENTS IN LC-MS Brief History of LC-MSThe last twenty years has seen a dramatic increase in the capabilities of MS. At the beginning of this period the invention of fast atom bombardment (FAB), by Barber et al. in 1981, 1) enabled easier analysis of involatile and thermally unstable molecules, especially those of biological interest. It may be argued that this technique acted as a catalyst for the development of other ionization techniques, such as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), applicable to such molecules.The combination of liquid chromatographic techniques with MS has been an important development. Early interfaces were concerned with coping with the potential of 1 l/min vapour in the MS ionisation source vacuum that would be generated by eluent from typical analytical columns flowing at 1 ml/min. This was achieved by evaporating solvent on a heated moving belt, 2,3) or the use of very low flows, such as direct liquid introduction 4,5) and continuousflow FAB (CF-FAB).6) Thermospray 7) and particle beam 8) interfaces were improved methods during the 1980s.Atmospheric Pressure Ionization (ESI and APCI) Over the last decade, ESI and atmospheric pressure chemical ionization (APCI), have become the dominant techniques superseding thermospray etc. and are likely to remain so for the foreseeable future being inherently the most suitable for analytes in solution presented to the MS. ESI was originally proposed by Dole,9) who suggested using charged droplets as a source of ions for MS and Fenn 10) pioneered its development as an ionization source for MS, leading to the first commercially available instrument in 1989.In essence, the electrospray process involves producing a fine spray of ionized droplets from the outlet of a capillary carrying a liquid stream, which may be eluent from HPLC, CE, CEC or direct infusion of sample solution. This is achieved by applying a high voltage (typically 3-5 kV) to the outlet of the capillary at the spray tip, which creates a high electric potential and causes the production of a fine mist of droplets. This occurs at atmospheric pressure, hence the term atmospheric pressure ionization (API), is used. Thi...

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In vitro and in vivo metabolism of 5,10,15,20-tetra (m-hydroxyphenyl)chlorin in rats and humans

Cai

Wang

Luo

et al. 1999

Biomed. Chromatogr.

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Identification of photochemical oxidation products of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin by on-line high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

Cited by 26 publications

References 4 publications

Matrix-assisted laser desorption/Ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry: a method to characterize temoporpfin photoproducts

Matrix-assisted laser desorption/Ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry: a method to characterize temoporpfin photoproducts

Current Developments in LC-MS for Pharmaceutical Analysis

In vitro and in vivo metabolism of 5,10,15,20-tetra (m-hydroxyphenyl)chlorin in rats and humans

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