Photodegradation of Chlorpromazine Hydrochloride

Felmeister, Alvin; Discher, Clarence A.

doi:10.1002/jps.2600530712

Cited by 58 publications

(18 citation statements)

References 8 publications

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“…Great care was taken to avoid contact with light because of possible photodecomposition exhibited by the phenothiazines (8). All surface-tension data are expressed in terms of surface pressure, K , which is the difference between the surface tension of the solvent and that of a given solution being measured.…”

Section: Methodsmentioning

confidence: 99%

Effect of Chemical Modification on the Surface Activity of Some Phenothiazine Derivatives

Zografi¹,

Munshi²

1970

Journal of Pharmaceutical Sciences

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Section: Methodsmentioning

confidence: 99%

Effect of Chemical Modification on the Surface Activity of Some Phenothiazine Derivatives

Zografi¹,

Munshi²

1970

Journal of Pharmaceutical Sciences

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“…This fact is mainly due to the spectrum of experimental conditions and initial drug concentration used in each study. Felmeister and Discher (22) studied the photodecomposition of CPZ‐HCl under aerobic and anaerobic conditions at 253.5 nm. For the kinetic studies and photodestruction quantum yield determination, they used microirradiation to excite its π→π* transition.…”

Section: Introductionmentioning

confidence: 99%

Photodegradation of 2‐chloro Substituted Phenothiazines in Alcohols

García

Piñero

Oyola

et al. 2009

Photochem & Photobiology

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The mechanisms that trigger the phototoxic response to 2-chlorophenothiazine derivatives are still unknown. To better understand the relationship between the molecular structure of halogenated phenothiazines and their phototoxic activity, their photophysics and photochemistry were studied in several alcohols. The photodestruction quantum yields were determined under anaerobic conditions using monochromatic light (313 nm). Absorption-and emission-spectroscopy, 1 H-and 13 C-NMR and GC-MS were used to characterize the photoproducts and reference compounds. An electron transfer mechanism had been previously proposed by Bunce et al. (J. Med. Chem. 22,[202][203][204] to explain the large difference between the photodestruction quantum yield of 2-chlorpromazine (u = 0.46) and 2-chlorphenothiazine (u = 0.20). According to these authors, the alkylamino chain transfers an electron to the phenothiazine moiety. Our results demonstrate that this mechanism is incorrect, because the photodestruction quantum yields of all chlorinated derivatives of this study are the same under the same conditions of solvent and irradiation wavelength. The quantum yield has no dependence on the 10-substituent, but it depends on the solvent. The percentage of each photoproduct, on the other hand, strongly depends on that substituent, but not very much on the solvent. Finally, it is demonstrated that the phototoxic effect of chlorinated phenothiazines is not related to the photodechlorination, although both processes share the same transient.

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“…The changes were perceived from indirect measurements that suggested the formation of radicals leading to the substitution at the sulfur atom (sulfoxides) and loss of the chloride at C-2 forming PZ. These changes were also perceived as “destruction” of the CPZ molecule, and the use of light to bring about this “destruction” was termed “photolysis” [27], [34], [35], [49]. Nevertheless, because the energy of a laser beam is thousands of times greater than that generated by UV light sources, we considered the possibility that lasers could be used to rapidly modify molecules with prolongation of exposure to hours rather than nanoseconds [32] and perhaps be used to produce reactions not possible with routine pyrogenic techniques used in organic chemistry.…”

Section: Discussionmentioning

confidence: 99%

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

et al. 2013

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IntroductionPhenothiazines when exposed to white light or to UV radiation undergo a variety of reactions that result in degradation of parental compound and formation of new species. This process is slow and may be sped up with exposure to high energy light such as that produced by a laser.MethodsVarying concentrations of Chlorpromazine Hydrochloride (CPZ) (2–20 mg/mL in distilled water) were exposed to 266 nm laser beam (time intervals: 1–24 hrs). At distinct intervals the irradiation products were evaluated by spectrophotometry between 200–1500 nm, Thin Layer Chromatography, High Pressure Liquid Chromatography (HPLC) - Diode Array Detection, HPLC tandem mass spectrometry, and for activity against the CPZ sensitive test organism Staphylococcus aureus ATCC 25923.ResultsCPZ exposure to 266 nm laser beam of given energy levels yielded species, whose number increased with duration of exposure. Although the major species produced were Promazine (PZ), hydroxypromazine or PZ sulfoxide, and CPZ sulfoxide, over 200 compounds were generated with exposure of 20 mg/mL of CPZ for 24 hrs. Evaluation of the irradiation products indicated that the bioactivity against the test organism increased despite the total disappearance of CPZ, that is due, most probably, to one or more new species that remain yet unidentified.ConclusionsExposure of CPZ to a high energy (6.5 mJ) 266 nm laser beam yields rapidly a large number of new and stable species. For biological grade phenothiazines (in other words knowing the impurities in the samples: solvent and solute) this process may be reproducible because one can control within reasonably low experimental errors: the concentration of the parent compound, the laser beam wavelength and average energy, as well as the duration of the exposure time. Because the process is “clean” and rapid, it may offer advantages over the pyrogenically based methods for the production of derivatives.

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Photodegradation of Chlorpromazine Hydrochloride

Cited by 58 publications

References 8 publications

Effect of Chemical Modification on the Surface Activity of Some Phenothiazine Derivatives

Effect of Chemical Modification on the Surface Activity of Some Phenothiazine Derivatives

Photodegradation of 2‐chloro Substituted Phenothiazines in Alcohols

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

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