Degradation studies on lurasidone hydrochloride using validated reverse phase HPLC and LC–MS/MS

The research aims to develop and validate a stability-indicating reverse phase high-performance liquid chromatography (RP-HPLC) method for Lurasidone hydrochloride, an antipsychotic drug derived from benzisothiazole derivatives.A Binary Gradient HPLC System with a PDA detector, C18 column (4.6 x 100 mm, 2.5 mm), and a Shimadzu 8040 series triple quadrupole mass analyzer with an electron spray ionizer was used for the LC-MS/MS analysis.The method was linear in the concentration range of 10-50 μg/mL with a correlation coefficient (r2) of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were 0.091 μg/mL and 0.275 μg/mL, respectively. Validation included accuracy, percentage recovery, robustness, system suitability, and interday and intraday precision. Forced degradation studies were conducted in acid, alkali, oxidative, neutral, and photolytic conditions after 1, 2, and 6 hours, and in oxidative conditions for 24 hours. Degraded products were evaluated on LC-MS (100 m/z to 550 m/z). Lurasidone was more susceptible to alkali hydrolysis, with fragmentation peaks at 109, 166, 220, and 317 m/z. and possible fragmentation pattern was also evaluated.This method is used for routine quality control analysis as a stability-indicating method of Lurasidone hydrochloride in pharmaceuticals, and the LC-MS data is used for evaluating stability and identifying drug intermediates. The research aims to develop and validate a stability-indicating reverse phase high-performance liquid chromatography (RP-HPLC) method for Lurasidone hydrochloride, an antipsychotic drug derived from benzisothiazole derivatives. A Binary Gradient HPLC System with a PDA detector, C18 column (4.6 x 100 mm, 2.5 mm), and a Shimadzu 8040 series triple quadrupole mass analyzer with an electron spray ionizer was used for the LC-MS/MS analysis. The method was linear in the concentration range of 10-50 μg/mL with a correlation coefficient (r2) of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were 0.091 μg/mL and 0.275 μg/mL, respectively. Validation included accuracy, percentage recovery, robustness, system suitability, and interday and intraday precision. Forced degradation studies were conducted in acid, alkali, oxidative, neutral, and photolytic conditions after 1, 2, and 6 hours, and in oxidative conditions for 24 hours. Degraded products were evaluated on LC-MS (100 m/z to 550 m/z). Lurasidone was more susceptible to alkali hydrolysis, with fragmentation peaks at 109, 166, 220, and 317 m/z. and possible fragmentation pattern was also evaluated. This method is used for routine quality control analysis as a stability-indicating method of Lurasidone hydrochloride in pharmaceuticals, and the LC-MS data is used for evaluating stability and identifying drug intermediates.

本研究旨在开发并验证一种稳定性指示型反相高效液相色谱（RP-HPLC）方法，用于盐酸鲁拉西酮的质量分析——盐酸鲁拉西酮是一种由苯并异噻唑衍生物衍生而来的抗精神病药物。本研究采用搭载光电二极管阵列（PDA）检测器的二元梯度高效液相色谱系统、C18色谱柱（4.6 × 100 mm，2.5 mm），以及配备电喷雾离子源的岛津（Shimadzu）8040系列三重四极杆质谱分析仪，开展液相色谱-串联质谱（LC-MS/MS）分析。该方法在10~50 μg/mL的浓度范围内呈现良好线性关系，相关系数（r²）为0.999。检测限（LOD）与定量限（LOQ）分别为0.091 μg/mL和0.275 μg/mL。方法学验证内容涵盖准确度、回收率、耐用性、系统适用性以及日间和日内精密度。本研究分别在酸性、碱性、氧化、中性及光解条件下开展强制降解试验，分别于1、2、6小时后取样分析，并在氧化条件下设置24小时的降解时长。采用扫描范围为100~550 m/z的液相色谱-质谱（LC-MS）对降解产物进行表征。结果显示，鲁拉西酮对碱性水解更为敏感，其降解产物的裂解峰分别位于109、166、220及317 m/z，本研究同时对其可能的裂解路径进行了探究。该方法可作为药物制剂中盐酸鲁拉西酮常规质量控制的稳定性指示分析手段，而LC-MS数据可用于药物稳定性评价及药物中间体的鉴定。本研究旨在开发并验证一种稳定性指示型反相高效液相色谱（RP-HPLC）方法，用于盐酸鲁拉西酮的质量分析——盐酸鲁拉西酮是一种由苯并异噻唑衍生物衍生而来的抗精神病药物。本研究采用搭载光电二极管阵列（PDA）检测器的二元梯度高效液相色谱系统、C18色谱柱（4.6 × 100 mm，2.5 mm），以及配备电喷雾离子源的岛津（Shimadzu）8040系列三重四极杆质谱分析仪，开展液相色谱-串联质谱（LC-MS/MS）分析。该方法在10~50 μg/mL的浓度范围内呈现良好线性关系，相关系数（r²）为0.999。检测限（LOD）与定量限（LOQ）分别为0.091 μg/mL和0.275 μg/mL。方法学验证内容涵盖准确度、回收率、耐用性、系统适用性以及日间和日内精密度。本研究分别在酸性、碱性、氧化、中性及光解条件下开展强制降解试验，分别于1、2、6小时后取样分析，并在氧化条件下设置24小时的降解时长。采用扫描范围为100~550 m/z的液相色谱-质谱（LC-MS）对降解产物进行表征。结果显示，鲁拉西酮对碱性水解更为敏感，其降解产物的裂解峰分别位于109、166、220及317 m/z，本研究同时对其可能的裂解路径进行了探究。该方法可作为药物制剂中盐酸鲁拉西酮常规质量控制的稳定性指示分析手段，而LC-MS数据可用于药物稳定性评价及药物中间体的鉴定。