Prajapati Pintu, Haque Anzarul, Kalam Mohd Abul, Shah Shailesh
Department of Quality Assurance, Maliba Pharmacy College, Maliba Campus, Bardoli-Mahuva Road, Tarsadi, Mahuva, Surat, 394 350, Gujarat, India.
Central Laboratories Unit, Qatar University, 2713, Doha, Qatar.
Anal Sci. 2025 Mar;41(3):263-279. doi: 10.1007/s44211-024-00694-5. Epub 2024 Dec 8.
Nateglinide is an oral meglitinide that treats diabetes. Nateglinide was determined in several commercial formulations using chromatographic and spectrophotometric methods in published research. Quality-by-design approach was applied to develop the in-house nateglinide-loaded Solid Dispersion Adsorbate (SDA) for improving bioavailability and solubility. To determine nanogram-level nateglinide concentration for the in-house developed nateglinide-SDA pharmacokinetics required time-consuming and expensive hyphenated analytical techniques such as LC-MS or UPLC-MS. Hence, a sensitive spectrofluorophotometric method was developed to estimate nateglinide using NBD-Cl (7-chloro-4-nitrobenzoxadiazole) as the fluorophore. Microwave-aided chemical derivatization of nateglinide with NBD-Cl sped up sample analysis. Chemical reaction solvents were eco-friendly to safeguard aquatic life and environment. The chemical process was optimized by quality by design approach using screening design and response surface modelling. The fluorescence intensity of nateglinide was found to be linear over the concentration range of 20-250 ng/mL with a correlation coefficient of 0.9978. The limits of detection and quantification were found to be 10 and 20 ng/mL respectively. Precision and robustness investigations of the spectrofluorimetric method showed less than 2% relative standard deviations. Nateglinide-SDA drug-release study and pharmacokinetics were performed using the sensitive spectrofluorophotometric method. The in-house developed nateglinide-SDA released 95% of the drug in 30 min time duration. In-house-developed nateglinide-SDA has 1.5 times the oral bioavailability of commercial formulations due to in-vivo absorption. The published analytical methods were compared to the enhanced-spectrofluorophotometric method for user-friendliness, efficiency, cost-of-analysis, and environmental friendliness. The proposed sensitive-spectrofluorophotometric method was found to be robust, rapid, eco-friendly, cost-effective, and simple for the estimation of nateglinide.
那格列奈是一种治疗糖尿病的口服格列奈类药物。在已发表的研究中，采用色谱法和分光光度法对几种市售制剂中的那格列奈进行了测定。采用质量源于设计的方法开发了自制的载那格列奈固体分散吸附剂（SDA），以提高生物利用度和溶解度。为了测定自制的那格列奈-SDA药代动力学中纳克级的那格列奈浓度，需要耗时且昂贵的联用分析技术，如液相色谱-质谱联用（LC-MS）或超高效液相色谱-质谱联用（UPLC-MS）。因此，开发了一种灵敏的荧光分光光度法，使用7-氯-4-硝基苯并恶二唑（NBD-Cl）作为荧光团来测定那格列奈。那格列奈与NBD-Cl的微波辅助化学衍生化加快了样品分析。化学反应溶剂对生态友好，可保护水生生物和环境。采用筛选设计和响应面建模的质量源于设计方法对化学过程进行了优化。发现那格列奈的荧光强度在20-250 ng/mL浓度范围内呈线性，相关系数为0.9978。检测限和定量限分别为10 ng/mL和20 ng/mL。荧光分光光度法的精密度和稳健性研究表明相对标准偏差小于2%。使用灵敏的荧光分光光度法进行了那格列奈-SDA药物释放研究和药代动力学研究。自制的那格列奈-SDA在30分钟内释放了95%的药物。由于体内吸收，自制的那格列奈-SDA的口服生物利用度是市售制剂的1.5倍。将已发表的分析方法与增强荧光分光光度法在用户友好性、效率、分析成本和环境友好性方面进行了比较。结果发现，所提出的灵敏荧光分光光度法用于那格列奈的测定具有稳健、快速、生态友好、成本效益高和操作简单的特点。
