Identification, isolation and characterization of impurities of clindamycin palmitate hydrochloride.

Clindamycin palmitate hydrochloride is a water soluble hydrochloride salt of the ester of clindamycin and palmitic acid. It is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Total 12 impurities at levels ranging from 0.05% to 0.5% were detected by isocratic reverse-phase high performance liquid chromatography (HPLC) using RI detector. The molecular weights of impurities were determined by LC-MS analysis. Two impurities were starting materials and the remaining impurities were isolated from crude samples/enriched mother liquors using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, clindamycin palmitate sulphoxides alpha-/beta-isomers (impurity I); clindamycin laurate (impurity II); lincomycin palmitate (impurity III); clindamycin myristate (impurity IV); epiclindamycin palmitate (impurity V); clindamycin palmitate 3-isomer (impurity VI); clindamycin pentadecanoate (impurity VII); clindamycin B-palmitate (impurity VIII); clindamycin heptadecanoate (impurity IX) and clindamycin stearate (impurity X). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and formation of these impurities have been discussed in detail.

Identification, isolation, synthesis and characterization of impurities of quetiapine fumarate.

In the process for the preparation of quetiapine fumarate (1), six unknown impurities and one known impurity (intermediate) were identified ranging from 0.05-0.15% by reverse-phase HPLC. These impurities were isolated from crude samples using reverse-phase preparative HPLC. Based on the spectral data, the impurities were characterized as 2-[4-dibenzo[b,f][1,4]thiazepine-11-yl-1 -piperazinyl]1 -2-ethanol (impurity I, desethanol quetiapine), 11-[(N-formyl)-1-piperazinyl]-dibenzo[b,f][1,4]thiazepine (impurity II, N-formyl piperazinyl thiazepine), 2-(2-hydroxy ethoxy)ethyl-2-[2-[4-dibenzo[b,f][1,4]thiazepine-11- piperazinyl-1-carboxylate (impurity III, quetiapine carboxylate), 11-[4-ethyl-1-piperazinyl]dibenzo [b,f][1,4] thiazepine (impurity IV, ethylpiperazinyl thiazepine), 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]1-ethyl ethanol [impurity V, ethyl quetiapine), 1,4-bis[dibenzo[b,f][1,4]thiazepine-11-yl] piperazine [impurity VI, bis(dibenzo)piperazine]. The known impurity was an intermediate, 11-piperazinyldibenzo [b,f][1,4]thiazepine (piperazinyl thiazepine). The structures were established unambiguously by independent synthesis and co-injection in HPLC to confirm the retention times. To the best of our knowledge, these impurities have not been reported before. Structural elucidation of all impurities by spectral data (1H NMR, 13C NMR, MS and IR), synthesis and formation of these impurities are discussed in detail.

Identification, isolation and characterization of potential degradation product in risperidone tablets.

One unknown impurity (degradation product) present at a level below 0.1% in the initial samples increased to a level of 0.5% in 6M/40 degrees C/75% RH stability samples of risperidone tablets was detected by gradient reverse-phase high-performance liquid chromatography (HPLC). This impurity was isolated using reverse-phase preparative liquid chromatography. Based on the spectral data the structure of this impurity is characterized as 3-[2-[4-[6-fluoro-1,3-benzoxazol-2-yl]piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a] pyrimidin-4-one. Structural elucidation of this impurity by spectral data ((1)H NMR, (13)C NMR, DEPT, MS and IR), formation and mechanism has been discussed in detail.

Impurity profile study of zaleplon.

Zaleplon is a pyrazolopyrimidine derivative and possesses sedative and hypnotic properties. Seven unknown impurities in zaleplon bulk drug at levels below 0.1% were detected by reverse-phase high performance liquid chromatography (HPLC). The starting material, 3-amino-4-cyanopyrazole and an intermediate, N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]-phenyl]-N-ethylacetamide (DOPEA) were also present in the sample at a level below 0.1%. The molecular weights of impurities were determined by LC-MS analysis. These impurities were isolated from crude samples of zaleplon using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, N-(3-(3-(4-amino-2H-pyrazolo [3,4-d]pyrimidin-6-yl) pyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N-ethylacetamide (impurity I); N-[3-(3-carboxamidopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (impurity II); N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide (impurity III); N-[3-(3-cyanopyrazolo [1,5-a]pyrimidin-7-yl)phenyl]-N-methylacetamide (impurity IV); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-5-yl)phenyl]-N-ethylacetamide (impurity V); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl]-N-ethylamine (impurity VI); N-[3-(3-cyano-6-[(E)-3-((N-ethyl-N-acetyl)amino)phenyl-3-oxoprop-1-enyl] pyrazolo[1,5-a]pyrimidin-7-yl) phenyl]-N-ethylacetamide (impurity VII). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and formation of these impurities are discussed in detail.