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.
Bharathi
Ch
Ch
A.P.L. Research Centre, 313 Bachupally, Hyderabad 500072, India.
Prabahar
K Joseph
KJ
Prasad
Ch S
ChS
Kumar
M Saravana
MS
Magesh
S
S
Handa
V K
VK
Dandala
Ramesh
R
Naidu
A
A
D000081:Acetamides / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004340:Drug Contamination; D006993:Hypnotics and Sedatives / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D008970:Molecular Weight; D011743:Pyrimidines / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature
D000081:Acetamides; D006993:Hypnotics and Sedatives; D011743:Pyrimidines; C085665:zaleplon