Kowtharapu Leela Prasad, Katari Naresh Kumar, Sandoval Christian A, Konduru Naresh, Muchakayala Siva Krishna, Pydimarry Surya Prakash Rao, Jonnalagadda Sreekantha Babu
Analytical Development Department, Shenzhen DEC Pharmaceutical Co., Ltd., Shenzhen 518000, China.
Department of Chemistry, School of Science, GITAM Deemed to be University, Hyderabad, Telangana 502329, India.
ACS Omega. 2023 Jun 8;8(24):21485-21492. doi: 10.1021/acsomega.3c00311. eCollection 2023 Jun 20.
This study evaluates the unknown qualitative (Q1) and quantitative (Q2) formulas for nasal spray and ophthalmic solution formulations of olopatadine HCl by classical and instrumental techniques to match the generic formula with reference-listed drugs to avoid clinical study. Reverse engineering of olopatadine HCl nasal spray 0.6% and ophthalmic solution 0.1, 0.2% formulations was accurately quantified using a simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) method. Both formulations possess similar components, namely ethylenediaminetetraacetic acid (EDTA), benzalkonium chloride (BKC), sodium chloride (NaCl), and dibasic sodium phosphate (DSP). These components were qualitatively and quantitatively determined using the HPLC, osmometry, and titration techniques. With derivatization techniques, EDTA, BKC, and DSP were determined by ion-interaction chromatography. NaCl in the formulation was quantified by measuring the osmolality and using the subtraction method. A titration method was also used. All the employed methods were linear, accurate, precise, and specific. The correlation coefficient was >0.999 for all components in all the methods. The recovery results ranged from 99.1 to 99.7% for EDTA, 99.1-99.4% for BKC, 99.8-100.8% for DSP, and 99.7-100.1% for NaCl. The obtained % relative standard deviation for precision was 0.9% for EDTA, 0.6% for BKC, 0.9% for DSP, and 1.34% for NaCl. The specificity of the methods in the presence of other components, diluent, and the mobile phase was confirmed, and the analytes were specific.
本研究通过经典和仪器技术评估盐酸奥洛他定鼻喷雾剂和眼药水制剂的未知定性（Q1）和定量（Q2）配方，以使仿制药配方与参比上市药品相匹配，从而避免进行临床研究。采用简单且灵敏的反相高效液相色谱（HPLC）方法对0.6%盐酸奥洛他定鼻喷雾剂以及0.1%、0.2%眼药水制剂进行逆向工程，实现了准确的定量分析。两种制剂具有相似的成分，即乙二胺四乙酸（EDTA）、苯扎氯铵（BKC）、氯化钠（NaCl）和磷酸氢二钠（DSP）。使用HPLC、渗透压测定法和滴定技术对这些成分进行了定性和定量测定。通过衍生化技术，采用离子相互作用色谱法测定EDTA、BKC和DSP。制剂中的NaCl通过测量渗透压并使用减法进行定量。还使用了滴定法。所有采用的方法均具有线性、准确性、精密度和特异性。所有方法中所有成分的相关系数均>0.999。EDTA的回收率结果为99.1%至99.7%，BKC为99.1% - 99.4%，DSP为99.8% - 100.8%，NaCl为99.7% - 100.1%。所获得的精密度%相对标准偏差，EDTA为0.9%，BKC为0.6%，DSP为0.9%，NaCl为1.34%。证实了这些方法在存在其他成分（稀释剂和流动相）时的特异性，且分析物具有特异性。
