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-piperazinyl-dibenzo [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.
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Document Type: Research Article
Affiliations:1: Aurobindo Pharma Ltd. Research Centre, Bachupally, Hyderabad, India 2: Aurobindo Pharma Ltd. Research Centre, Bachupally, Hyderabad, 500072, India, Email: [email protected]3: J. N. T. University, Kukatpally, Hyderabad, India
Publication date: January 1, 2008
Pharmazie is a leading journal in the field of pharmaceutical sciences. As a peer-reviewed scientific journal, Pharmazie is regularly indexed in the relevant databases like Web of science, Journal Citation Reports and many others. The journal is open for submissions from the whole spectrum of pharnaceutical sciences including Pharmaceutical Chemistry, Experimental and Clinical Pharmacology, Drug Analysis, Pharmaceutics, Pharmaceutical Biology, Clinical Pharmacy etc.
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The two synthesis essay questions below are examples of the question type that has been one of the three free-response questions on the AP English Language and Composition Exam as of the May 2007 exam. The synthesis question asks students to synthesize information from a variety of sources to inform their own discussion of a topic. Students are given a 15-minute reading period to accommodate the additional reading required for the question.
Below is a sample synthesis essay question, sample scoring guidelines, comments from the Chief Reader about the sample student essays, seven sample student responses, and scoring commentary for each sample.
Approximately 300 AP English Language and Composition students from eight schools in New York, Maine, Texas, Tennessee, Washington, Florida, and New Mexico wrote responses to this synthesis topic. Students from these schools were given a 15-minute reading period followed by a 40-minute writing period in which to complete the sample synthesis assignment.
An additional sample synthesis essay question is provided here.