Analysis of docosanol using GC/MS:Method development,validation,and application to ex vivo human skin permeation studies / 药物分析学报

Docosanol is the only US Food and Drug Administration(FDA)approved over-the-counter topical product for treating recurrent oral-facial herpes simplex labialis.Validated analytical methods for docosanol are required to demonstrate the bioequivalence of docosanol topical products.A gas chromatography/selected ion monitoring mode mass spectrometry(GC/SIM-MS)method was developed and validated for docosanol determination in biological samples.Docosanol and isopropyl palmitate(internal standard)were separated on a high-polarity GC capillary column with(88％cyanopropy)aryl-polysiloxane employed as the stationary phase.The ions of m/z 83 and 256 were selected to monitor docosanol and isopropyl palmitate,respectively;the total run time was 20 min.The GC/SIM-MS method was validated in accordance with US FDA guidelines,and the results met the US FDA acceptance criteria.The docosanol calibration standards were linear in the 100-10000 ng/mL concentration range(R2＞0.994).The recoveries for docosanol from the receptor fluid and skin homogenates were＞93.2％and＞95.8％,respectively.The validated method was successfully applied to analyze ex vivo human cadaver skin permeation samples.On applying Abreva?cream tube and Abreva?cream pump,the amount of doco-sanol that penetrated human cadaver skin at 48 h was 21.5±7.01 and 24.0±6.95 ng/mg,respectively.Accordingly,we concluded that the validated GC/SIM-MS was sensitive,specific,and suitable for quantifying docosanol as a quality control tool.This method can be used for routine analysis as a cost-effective alternative to other techniques.

Electret enhances transdermal drug permeation.

Electrets are polymeric discs that carry semi permanent electrostatic charge. These provide electrostatic potentials in the range of 500 to 3,000 V. In the current work, the effect of electret exposure on the skin permeability was investigated. Transdermal transport studies were carried out across porcine epidermis in Franz diffusion cells. Salicylic acid, fluorescein labeled dextrans (FD) and propofol were used as test diffusants. The ability of electret to enhance the transdermal permeation of salicylic acid was studied in vivo in Sprague Dawley rats. Electret enhanced the permeability of porcine epidermis to salicylic acid. The enhancement factor increased with the surface voltage, however it was independent of the nature of charge (+ or -). The enhancement by electret was cut-off at 1 kDa, as interpreted by studying the transport of FD. The electrets decreased the permeability of skin to propofol, a lipophilic diffusant. Pretreatment of porcine epidermis enhanced the iontophoretic transport of salicylic acid, whereas the same did not enhance the transport of salicylic acid by electroporation. It is most likely that electret exposure renders the lipid domains of stratum corneum more permeable to polar molecules and in turn hampers the diffusion of nonpolar diffusant.