Gas chromatography/trace analysis of derivatized azelaic acid as a stability marker

Abstract

Azelaic acid, a naturally occurring saturated dicarboxylic acid, is found in many topical formulations for its various medical benefits or as a byproduct of the oxidative decomposition of unsaturated fatty acids. The poor volatility of azelaic acid hinders its applicability in GC analysis. Therefore, azelaic acid was derivatized by methylation and silylation procedures to enhance its volatility for GC analysis. Accordingly, dimethyl azelate (DMA) and di(trimethylsilyl) azelate were synthesized and characterized by GC-MS. Subsequently, a GC with flame ionization detection method was developed and validated to analyze trace amounts of azelaic acid in some marketed skin creams. Unlike DMA, di(trimethylsilyl) azelate was chemically unstable and degraded within few hours. Nonane was used as a stable internal standard. Variability due to derivatization and extraction was controlled by a standard addition procedure. DMA analysis was linear in a wide concentration range (100 ng/mL to 100 mg/mL). Moreover, the method was accurate (96.4-103.4%) and precise with inter- and intraday variability <2.0% and LOQ and LOD of 100 and 10 ng/mL, respectively.

A prodrug approach to enhance azelaic acid percutaneous availability

“…It was noted that percentage recovery was almost 100% in all situations; hence, DEA was quite resistant to chemical hydrolysis. The results are in good agreement with earlier reported results by Alzweiri et al 21 Chemical stability of aliphatic diesters was reported and studied using FT-IR and NMR by Raghunanan and Narine 35 . It was reported that when the hydrocarbon chain between the two carbonyl groups gets longer, ester bond becomes more stable 35 .…”

“…Preparation and stability of diethyl azelate (DEA) DEA prodrug was synthesized according to the general procedure described by Alzweiri et al for the preparation of dimethyl azelate (DMA) 21 . Ethanol was used for the preparation of DEA, and an oily faint-yellow liquid was obtained.…”

“…Method of analysis DEA samples were analyzed using a validated GC-FID methodology according to Alzweiri et al 21 Briefly, DEA samples were mixed with 30 ll DMA as internal standard. The mixture was divided into two equivalent portions.…”

“…Many prodrugs were synthesized and successfully improved the bioavailability of 5-fluorouracil, acetylsalicylic acid, metronidazole, and many others [18][19][20] . Methanolic ester of azelaic acid was synthesized previously by our research group to facilitate azelaic acid detection on GC-FID (Gas Chromatography-Flame Ionization Detector) 21 . In addition, ethanolic ester of azelaic acid was also synthesized to study its impact on cytotoxic activity of azelaic acid 22 .…”

A Validated Stability-indicating RP-HPLC Method for Analysis of Azelaic Acid in Pharmaceuticals

“…These include spectrophotometric analysis employing UV/fluorescent detector or by utilizing thin layer chromatography, gas chromatography and liquid chromatography-mass spectrometry. These techniques either follow pre-column derivatization approach via 1-leucine-4-methyl-7-coumarinylamide [12] , methyl methoxy coumarin [13] , methylation/salylation [14] , 4-bromophenacylbromide/phenacetyl bromide [15,16] , 2-bromoacetyl-6-methoxynaphthalene [17] or on-column derivatization via charged dye [18] . Most of these methods are sensitive enough for the quantitative analysis of lower concentrations of AZA.…”