Study On The Quality Standard Of Radiation Sensitizer YABQ API

Cancer has become a major killer of threat to human life, health and safety,radiotherapy is currently the main treatment. After long-term domestic and foreign scholars study found that a chemical substance that is radiosensitizer, not only can improve radiosensitization of cancer cells, it will not damage the body’s blood and immune system function.Benzotriazine derivative YABQ as a new radiation sensitizer, a nitro group to get rid of the structure, the nucleus is no longer a five-membered nitrogen-containing rings,and greatly reduce the side effects, unique and novel chemical structures; benzotriazine derivatives YABQ in a very short time after low doses of radiation, can improve the sensitivity of lack of oxygen in the cells, improve the ability of killing tumor cells, is effective and has a dual role. This paper established a method for the determination of benzo-triazine derivative YABQ.Analysis of drug quality inspection standards, its purpose is to demonstrate test methods meet the test requirements. Drug quality standard requires analytical method validation. In this study, respectively, from the physical and chemical properties,identification, determination, related substances analysis, aspects of residual organic solvents, stability studies on radiation sensitizer YABQ quality control is benzo-triazine derivative of YABQ packaging, transport, storage and production quality control to provide a scientific basis.1 physicochemical properties and inspectionFor YABQ traits, solubility, hygroscopicity, melting, etc. were examined, according to "Chinese Pharmacopoeia" appendix requirements of the three batches of samples(batch number: 20140410,20140416,20140424) were inorganic inspection results show that chlorine YABQ three batches of samples compounds, heavy metals, arsenic salts test results are in line with Pharmacopoeia.2 YABQ establish five kinds of identification methodsEstablished five identification methods benzotriazine derivative YABQ of: ultraviolet spectrophotometry,high performance liquid chromatography,high performance liquid chromatography with evaporative light scattering detector,high performance liquid chromatography and mass spectrometry, thin layer chromatography for YABQ drug three batches of samples(batch number: 20140410,20140416,20140424) and controls wereidentified. The results showed that three batches of samples and reference YABQ are displayed as the same substance.3 determination to establish analytical methodsFor HPLC-DAD and HPLC-ELSD analysis radiosensitizer YABQ Determination were compared. The results showed that, HPLC-ELSD the peak shape is not easy to control, easy top peak bifurcation, optimized airflow and temperature, reduced concentration, due to the lack of instrument design, no much has changed; and HPLC-DAD of the peak shape good method reproducibility is good, and simple operation,low cost, the content of the final drug YABQ of measurement and analysis decided to use HPLC-DAD.The establishment of a radiosensitizing drug benzotriazine derivative YABQ Determination by HPLC, chromatographic conditions: Diamonsil C18(250 mm × 4.6mm, 5μm) column; mobile phase(methanol: 22%, 0.1% formic acid: 78%); detection wavelength: 266 nm, flow rate: 1m L / min, column temperature: 30 ℃, injection volume:10μL. The method validation test results: YABQ detection limit 8ng, quantitation limit is24 ng, 7~84μg / m L(r = 0.9992) in the linear range of the instrument precision of the method, day precision, accuracy and repeatability day the RSD value not greater than 2%.The results show that this method can be benzotriazine derivative YABQ used to determine the content. This product calculated on dry goods content shall not be less than98.0%.4 related substance analysisBy HPLC analysis to establish a method for the determination of radiation sensitizer benzotriazine derivative YABQ related substances, the study examined under the influence of acid, alkali, oxidation, temperature and light conditions on the radiosensitizer YABQ.The results showed that benzotriazine derivative YABQ under high temperature and light conditions are no new stable degradation products. Under acidic and alkaline hydrogen peroxide for 30% of the degradation products, and degradation products by HPLC analysis YABQ better peak separation(separation greater than 1.5).Using HPLC, LC-MS for drug related substances were analyzed based on molecular fragment ion mass spectrometry were reasonable explanation, to infer about the substance contained in the synthesis.5 The establishment of five residual solvent analysis methodThe establishment of a radiation sensitizer benzotriazine derivative YABQ residual solvent such as acetone, pyridine and tetrahydrofuran headspace capillary gas chromatography(HS-GC) method. Chromatographic conditions: DB-WAX(30m ×0.45 mm, 0.85μm) capillary column; column temperature: initial temperature 50 ℃,maintained 6min, followed by 35 ℃ / min was raised to 200 ℃, 10 min maintained;Gasification chamber temperature: 200 ℃; FID detector temperature: 250 ℃; carrier gas:high purity nitrogen; column flow: 3.5m L / min; stigma pressure: 4psi; split ratio of 10: 1;air flow rate: 330 m L / min; hydrogen flow rate: 40 m L / min; auxiliary gas flow rate: 18 m L/ min; headspace vial temperature: 70 ℃; loop temperature: 80 ℃; belt temperature: 90 ℃;vial heating time: 10 min. The results show: acetone, pyridine and tetrahydrofuran separated within the concentration range of study and a good linear relationship, the average recovery of 95%-105% of the goods in pyridine and tetrahydrofuran residue not detected residual amount of acetone in the pharmacopoeia specified range.6 Stability6.1 Factors Affecting TestHigh temperature(60 ℃), humidity(92.5% ± 5%) and glare(4500lx ± 500lx)opening in 10 days condition, in the fifth day, the tenth day of each sampling, Stability YABQ drugs, observe the effects of factors that may exist and degradation pathways and degradation products YABQ stability. The results showed that benzotriazine derivative YABQ drug at a high temperature, high humidity, and bright light test conditions, the appearance and content of related substances stable no significant change within 10 days.6.2 acceleration testTake YABQ drug three batches of samples(batch number:20140410,20140416,20140424), simulated commercial packaging, accelerating at(40 ℃ ±2 ℃, 75% ± 5% relative humidity) Test conditions placed respectively at zero months,January February, March, June sampling test study YABQ stability, results showed benzotriazine derivative drug YABQ stable acceleration test for six months.6.3 Long-term testTake YABQ drug three batches of samples(batch number:20140410,20140416,20140424), simulated commercial packaging, under the test conditions 25 ℃ ± 2 ℃, 60% ± 10% relative humidity placed, respectively 0,3,6, 9, 12, 18,24, 36 months sampled for observation YABQ stability, provide the basis for an effectiveperiod of the drug. The results show, benzotriazine derivative drug YABQ stable under conditions of long-term testing of 6 months. Further analysis of the experiment is still ongoing.7 SummaryDrug Quality Standard is the national "drug approval approach" requirements developed. This paper established a method for the determination of YABQ, inferred related substances, through methodological study to prove the method of its determination to establish compliance with the requirements and YABQ the stability studies, residual solvent was measured for new drugs YABQ the registration application basis.