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Samer Housheh ¹, Saleh Trefi ², M. Fawaz Chehna ²

Affiliations
1 Department of Quality Control and Pharmaceutical Chemistry, Al-Andalus University, Tartous, SY
2 Department of Quality Control and Pharmaceutical Chemistry, University of Aleppo, Aleppo, SY

Abstract

The objective of the present work was to separate, identify and characterize the degradation products of Prasugrel hydrochloride under hydrolytic and oxidative stress conditions according to the International Conference on Harmonization (ICH) guideline Q1A (R2). The drug degraded under acidic, basic, and oxidative stress. Five degradation products were formed, which were separated using preparative TLC. Mass fragmentation pathway of the drug was first established with the help of GC/MS studies. The degradation products were subjected to FTIR and 1H NMR studies. The obtained mass spectral data were employed to characterize the degradation products and assign structures. The degradation products were identified as 5-(2- cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2(3H)-one, 5-(2-cyclopropyl- 1-(2-fluorophenyl)-2-oxoethyl)-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one, 2-acetoxy-5-(2-cyclopropyl- 1-(2-fluorophenyl)-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 5-oxide, 1-cyclopropyl-2-(2- fluorophenyl)ethane-1,2-dione and 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate.

Keywords

Stress Studies, Prasugrel Hydrochloride, GC/MS, FTIR, 1H NMR, Degradation Products.

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Samer Housheh ¹

Affiliations
1 Quality Control and Pharmaceutical Chemistry, Al -Andalus University, SY

Abstract

An accurate, sensitive, precise and stability indicating (in accordance with ICH guidelines) reversed phase high performance liquid chromatographic (RP-HPLC) method of analysis of Azithromycin was developed and validated. The chromatographic conditions comprised of a reversible phase C8 column (250 × 4.6 mm, 5μ) with a mobile phase consisting of a mixture of dipotassium hydrogen Phosphate and Acetonitrile in the ratio of 65:35 at pH 6.5 adjusted with phosphoric acid. Flow rate was 1.5 ml/min, the detection was carried out at 200 nm and the retention time of Azithromycin was 2.99 min. Azithromycin was subjected to acid and alkali hydrolysis, oxidation and photochemical degradation. The method was validated for accuracy, precision and robustness. The results indicate that the drugs are susceptible to degradation in different conditions. All the peaks of degraded products were resolved from the active pharmaceutical ingredient with significant different retention times. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating one.

Keywords

RP-HPLC, Azithromycin, Validation, Degradation, Stability Indicating.

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