Objective: To establish normal phase high performance liquid chromatography(NP-HPLC) for the quantitative analysis of enantiomeric impurities in tadalafil starting material D-tryptophan methyl ester hydrochloride. Methods: Chiralpak IC (250 mm×4.6 mm, 5 μm) chromatographic column, a starch derivative chiral column, was used for isocratic elution with n-hexane-isopropanol-diethylamine(60:40:0.1) as the mobile phase, the flow rate was 0.9 mL·min-1, the column temperature was 40 ℃, the detection wavelength was 279 nm, and the injection volume 10 μL. The external standard method was used to calculate the enantiomeric impurity content. Results: The method was highly specific. The enantiomeric impurities had a good linear relationship within the concentration range of 0.15-5.00 μg·mL-1.The detection limit and the limit of quantification were 0.05 μg·mL-1 and 0.15 μg·mL-1, respectively. The RSD of the precision and stability experiments were all less than 5 %.The sample recovery rates at the three concentration levels of 80%, 100% and 120% were between 99.0% and 100.0%. Four batches of starting material samples were measured; the mass concentration of enantiomeric impurities was 0.19%-0.22%, which met the quality requirements. Conclusion: The method is fast, sensitive and accurate, and is suitable for the quantitative analysis and quality control of enantiomeric impurities in tadalafil starting materials.
FENG Jing, SHAO Hui-hui, ZHANG Wen-xuan, ZHANG Jie, WANG Yue, WU Song, YANG Qing-yun
. Determination of enantiomer impurities in tadalafil starting material by NP-HPLC*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(7)
: 1178
-1185
.
DOI: 10.16155/j.0254-1793.2022.07.10
[1] 宋秋韵. 他达拉非单药与联合贝前列素治疗中重度先天性心脏病相关性肺动脉高压临床观察[D].南宁: 广西医科大学, 2018
SONG QY. The Observation of Tadalafil Monotherapy and Comboned with Beraprost in the Treatment of Moderate-Severe Pulmonary Arterial Hypertension Associated with Congenital Heart Disease[D].Nanning: Guangxi Medical University, 2018
[2] 林升汉, 黄卫, 孙占玉, 等. 他达拉非联合坦索罗辛治疗FPKRP术后继发阴茎勃起功能障碍的临床观察[J].中国药房, 2017, 28(21): 2944
LIN SH, HUANG W, SUN ZY, et al. Clinical observation of tadalafil combined with tamsulosin in the treatment of ED patients after FPKRP[J].China Pharm, 2017, 28(21): 2944
[3] 杨传伟, 刘杰, 刘文涛, 等. 公斤级他达拉非的合成[J].中国医药工业杂志, 2018, 49(12): 48
YANG CW, LIU J, LIU WT, et al. Synthesis of tadalafil in kilogram scale[J].Chin J Pharm, 2018, 49(12): 48
[4] SHI XX, LIU SL, WEI X, et al. Highly stereoselective Pictet-Spengler reaction of d-tryptophan methyl ester with piperonal: convenient syntheses of cialis (tadalafil), 12a-epi-cialis, and their deuterated analogues[J].Tetrahedron Asymmetry, 2008, 19(4):435
[5] BIDLINGMAIER B, UNGER KK, DOEHREN NV. Comparative study on the column performance of microparticulate 5-μm C18-bonded and monolithic C18-bonded reversed-phase columns in high-performance liquid chromatography[J].J Chromatogr A, 1999, 832(1-2):11
[6] 徐红, 侯健. 高效液相色谱的色谱柱的类型和流动相的选择方法[J].计量与测试技术, 2010, 37(2): 10
XU H, HOU J. The choicing ways of chromatographic column and mobilephase about HPLC[J].Metrol Meas Tech, 2010, 37(2): 10
[7] 赵双丽, 罗菲菲, 祝璐琪, 等. γ-氨基丁酸键合硅胶毛细管色谱柱填料的绿色制备及其分析性能研究[J].分析测试学报, 2019, 38(7): 865
ZHAO SL, LUO FF, ZHU LQ, et al. Green preparation of a γ-aminobutyric acid bonded silica packing material for capillary column and its performance evaluation[J].J Instrum Anal, 2019, 38(7): 865
[8] 温晓丽, 石辛孺, 海青梅, 等. 用Chiralpak IC柱分离4种碱性药物异构体[J].沈阳药科大学学报, 2018, 35(7): 563
WEN XL, SHI XR, HAI QM, et al. Enantioseparation of four basic drugs by Chiralpak IC column[J].J Shenyang Pharm Univ, 2018, 35(7): 563
[9] TONG Z, NGUYEN D, FRANCO P, et al. Cellulose tris(3,5-dichlorophenylcarbamate) immobilised on silica: a novel chiral stationary phase for resolution of enantiomers [J].J Pharm Biomed Anal, 2008, 46(5): 882
[10] TONG Z, NGUYEN D, FRANCO P. Enantiomer resolution screening strategy using multiple immobilised polysaccharide-based chiral stationary phases[J].J Chromatogr A, 2008, 1191(1-2): 214
[11] OLAMOTO Y, KAIDA Y. Resolution by highperformance liquid chromatography using polysaccharide carbamates and benzoates as chiral stationary phase[J].J Chromatogr A, 1994, 666(6): 403
[12] 杨庆云, 王志鹏, 邓愉凤, 等. 正相高效液相色谱法拆分普拉克索对映异构体[J].药物分析杂志, 2014, 34(11): 2005
YANG QY, WANG ZP, DENG YF, et al. Chiral separation of pramipexole enantiomers by normal phase high performance liquid chromatography[J].Chin J Pharm Anal, 2014, 34(11): 2005
[13] 曹正, 李水军, 沈敏, 等. 液相色谱串联质谱临床检测方法的开发与验证[J].检验医学, 2019, 34(3): 189
CAO Z, LI SJ, SHEN M, et al. Consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories[J].Lab Med, 2019, 34(3): 189
[14] STAFFORD JD, MALONEY TD, MYERS DP, et al. A systematic approach to development of liquid chromatographic impurity methods for pharmaceutical analysis[J].J Pharm Biomed Anal, 2011, 56(2): 280
