Stress degradation studies on zolpidem tartrate using LC-DAD and LC-MS methods

Abstract

Summary. The present study was designed to characterize the possible degradation products of zolpidem tartrate under various stress conditions according to International Conference on Harmonization (ICH) guidelines Q1A(R2). After exposure to light, heat, hydrolysis, and oxidation, the drug significantly degraded under photolytic and acid/base hydrolytic conditions. Degradation resulted in the formation of four key degradants. Degradation products were resolved from each other and the drug by employing an isocratic elution method on Luna C 18 column with mobile phase consisting of methanol-10 mM ammonium acetate (68.4:31.6, v/v), wherein pH was adjusted to 5.4 with glacial acetic acid. To characterize the degradation products, a method was extended to LC-MS and a mass fragmentation pattern was established using single quadrupole. The degradants were identified as zolpacid, oxozolpidem, zolpaldehyde, and zolpyridine. Finally, the most possible degradation mechanism of zolpidem tartrate in different environments was proposed.

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

“…The solid form proved relatively stable, although photolytic degradation also occurred to a minor extent. Film coating of tablets inhibited this degradation pathway [ 27 ]. Unfortunately, 3D-printed tablets are not film coated, and as such, it is necessary to confirm the importance and to quantify the extent of the photolytic degradation pathway.…”

“…Major degradants were zolpacid (RRT 0.85) and zolpyridine (RRT 2.05), along with two unidentified degradants. These degradants most likely have oxygen bonded to the ZHT molecule on pyridine, forming N-oxide, or on the lateral methyl groups, forming methoxy groups, based on the DAD spectra and LC-MS data from Malsevic et al [ 27 ]. Their presence suggests a photolytic oxidation pathway causing zolpidem degradation in addition to hydrolysis.…”

“…Forced degradation by photolytic oxidation was performed on ZHT using a method as described by Malesevic et al [ 27 , 31 ]. Degradation of the API in solution and solid state in the presence or absence of light was investigated using HPLC-UV analysis.…”

“…In this study, zolpidem hemitartrate will be used as a BZRA to create a 3D-printed flexible dosage form to aid in withdrawal therapy. The stability of this API was already investigated by forced degradation studies [ 26 , 27 ], although only a limited number of studies utilizing ZHT to produce dosage forms was reported. Moreover, previous studies focused mainly on either increasing the drug dissolution rate or developing extended-release tablets, which were thought to be beneficial in terms of efficacy and patient compliance by supporting sleep maintenance [ 28 , 29 ].…”

Chemiluminescence System of Permanganate-Sulfite for Simple Determination of Zolpidem

“…Zolpidem undergoes oxidation by N-demethylation, N-oxidation, decarboxylation, and oxidation of methyl groups and hydroxylation of a position on the imidazolepyridine ring [42]. Oxidation products in weak oxidative medium are oxozolpidem, zolpaldehyde, zolpyridine [43] and in strong oxidation medium, the products are acid derivatives [44].…”