Aspirin in Dissolution Media

[syx]

Dear All,
We want to analyze Aspirin in aqueous dissolution media. Spectrophotometric method is used in original procedure (USP, BP), but we need more sensitive method because the composition of API in our tablets is lower. Aspirin is unstable in aqueous media and partially degrades to salicylic acid. So we found 2 peaks in chromatogram: Aspirin and Salicylic acid. We could calculate the peak of Salicylic acid but we couldn’t on Aspirin peak because the reference standard of Aspirin will be hydrolyzed too in the same media.
Aspirin in non-aqueous solvent was injected and the peak shape was different with Aspirin in dissolution media.
Should Aspirin be degraded completely to form Salicylic acid? Then from the calculation of Salicylic acid concentration we could get concentration of Aspirin using MW ratio. Is it OK?

Regards,
SYX

[HW Mueller]

Strange, Aspirin apparently survives the strongly acidic stomach...what media do you have to cause unstability? Strong base? My guess would be that Aspirin is easier to chromatograph than salicylic acid.

[Mark Tracy]

I have also done HPLC of aspirin. Salicylic acid is always present, and hydrolysis is easily observed over the course of a few hours even in deionized water. Storing aspirin in a moist atmosphere will induce hydrolysis; improperly stored it smells of acetic acid. So...
Make the stock acetylsalicylic acid in organic solvent, knowing that it will be contaminated with salicylic acid. Dilute immediately before injection. A refrigerated autosampler is nice to have. Measure the percent of salicylic acid in your aspirin standard, and if it is low enough just correct for it in the calculations. (Document your calculations!)

[syx]

It is dissolution test for Aspirin tablets. 0.1N HCl is used as media in acid stage. Though Aspirin will be survived in acidic media but Salicylic acid still occurs as degradation product in small portion. This condition will make a bias.

[HW Mueller]

So the kinetics are slow? I would expect the equilibrium, if there is a reaction in acid, to lie far to salicylic with all that water around, etc.

[syx]

In that monograph of USP, aspirin reference standard solution is made in chloroform – methanol – acetic acid glacial solvent (1). In other monograph, a mixture of acetonitrile and formic acid is used (2). Both solvents produce severe fronting peak due to solvent strength issue. Thus the mixture of DMSO and formic acid is used as solvent. The peak shape is better now.
Other parameter should be changed is wavelength. Wavelength of 280 nm is used in the monograph, but it less sensitive for salicylic acid. We tried to use 240 nm to get higher absorbance and sensitivity to salicylic acid. But the problem occurred with acetic acid in mobile phase in this wavelength. We tried to use other kind of acid to substitute acetic acid in mobile phase, but we found that DMSO gives disturbance in 240 nm too.
We decided to use other wavelength than 240 nm. Salicylic acid has another peak of spectrum in 304 nm, but aspirin (active substance) and benzoic acid (internal standard) did not have absorbance in this wavelength. For aspirin and benzoic acid, wavelength of 280 nm is still used, and then the wavelength is switched to 304 nm for salicylic acid.

Question:
Could we use a wavelength switch in a method using internal standard with different wavelength for the substance and internal standard?

Reference:
1. USP monograph for Acetaminophen and Aspirin Tablets
2. USP monograph for Aspirin Delayed Release Tablets

[oldtimer]

There is a publication for darvon related substances that includes a stable preparation for aspirin that prevents its degradation to salicylic acid. Depending on your sensitivity needs, the dilution in acetonitrile/formic acid/citric acid may reduce your aqueous component low enough to prevent aspirin degradation. (see publication: L. J. Burge and D. W. Raches, “A rapid HPLC assay for the determination of dextro-propoxyphene related substances in combination with aspirin, acetaminophen, and caffeine in tablet and capsule formulationsâ€