Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination
Yıl: 2021 Cilt: 18 Sayı: 3 Sayfa Aralığı: 66 - 75 Metin Dili: İngilizce DOI: 10.4274/tjps.galenos.2020.89725 İndeks Tarihi: 15-01-2022
Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination
Öz: Objectives: The aim of this study was to develop and optimize a simple, cost-effective, and robust high-performance liquid chromatography (HPLC) method by taking an experimental design approach to the assay and dissolution analysis of amlodipine besylate and enalapril maleate from a fixeddose combination tablet. Materials and Methods: The chromatographic analysis was performed on a C18 column (4.6x250 mm id., particle size of 5 μm). The injection volume was 5 μL, and the detection wavelength was 215 nm. A Box-Behnken design was used to test the robustness of the method. The flow rate (1, 1.2, and 1.4 mL/min), column temperature (25°C, 30°C, and 35°C), methanol ratio of the mobile phase (5, 10, and 15%), and pH of the mobile phase (2.8, 3, and 3.2) were selected as independent variables. The method was validated according to International Conference on Harmonization guidelines. Dissolution of the tablets was performed by using USP apparatus 2 and analyzed using the optimized HPLC method. Multivariate linear regression analysis and ANOVA were used in the statistical evaluation. Results: Linear models were fitted for all variables. The flow rate was the most significant factor affecting the APIs’ concentrations. The optimized method included the following parameters: Column temperature of 25°C, 10% methanol as the mobile phase, pH of 2.95, and flow rate of 1.205 mL/ min. Retention times were 3.8 min and 7.9 min for enalapril and amlodipine, respectively. The method was found to be linear in the range of 0.8-24 μg/mL (R2>0.999) and 1.6-48 μg/mL (R2>0.999) for amlodipine and enalapril, respectively. Both APIs were dissolved more than 85% within 10 min. Conclusion: The experimental design was proved as a useful tool for the determination and separation of enalapril maleate and amlodipine besylate in dosage forms. The optimized method can be used for in vitro performance and quality control tests of fixed-dose tablet combinations containing enalapril maleate and amlodipine besylate.
Anahtar Kelime: Amlodipin Besilat ve Enalapril Maleatın Sabit Dozlu Kombinasyondan Analizi için Deney Tasarımı Yoluyla Bir YBSK Yöntemi Geliştirilmesi ve Validasyonu
Öz: Amaç: Bu çalışmanın amacı, amlodipin besilat ve enalapril maleat içeren sabit dozlu kombinasyon tabletinden disolüsyon ve miktar tayini analizi için deney tasarımı yaklaşımı ile basit, ekonomik ve sağlam bir yüksek basınçlı sıvı kromatografisi (YBSK) yönteminin geliştirilmesi ve optimizasyonudur. Gereç ve Yöntemler: Kromatografik analiz C18 kolonda (4,6x250 mm id., 5 μm partikül çapı) gerçekleştirilmiştir. Enjeksiyon hacmi 5 μL ve dalga boyu 215 nm’dir. Yöntemin sağlamlığının test edilmesinde Box-Behnken tasarımı kullanılmıştır. Akış hızı (1, 1,2, ve 1,4 mL/dk), kolon sıcaklığı (25°C, 30°C ve 35°C), hareketli fazdaki metanol oranı (%5, %10 ve %15) ve hareketli fazın pH’sı (2,8, 3 ve 3,2) bağımsız değişkenler olarak seçilmiştir. Yöntemin validasyonu ICH kılavuzlarına göre gerçekleştirilmiştir. Tabletlerin çözünme hızı deneyleri USP cihaz 2 kullanılarak 75 devir/dk hızda gerçekleştirilmiştir. Çözünme hızı çalışması 0,1 N HCl’da 37±0,5°C’de yapılmış ve optimize edilen YBSK yöntemi ile analiz edilmiştir. İstatistiksel değerlendirmede çok değişkenli doğrusal regresyon analizi ve ANOVA testi kullanılmıştır. Bulgular: Tüm değişkenler için doğrusal modeller kullanılmıştır. Etkin madde konsantrasyonlarını etkileyen en anlamlı faktör akış hızıdır. Optimize edilen yöntem şu parametreleri içermektedir: 25°C kolon sıcaklığı, hareketli fazda %10 metanol oranı, 2,95 hareketli faz pH’sı ve 1,205 mL/dk akış hızı. Alıkonma zamanları enalapril ve amlodipine için sırasıyla 3,8 dk ve 7,9 dk olarak bulunmuştur. Yöntem amlodipin ve enalapril için sırasıyla 0,8-24 μg/mL (R2>0,999) ve 1,6-48 (R2>0,999) μg/mL aralıkta doğrusal bulunmuştur. Her iki etkin madde de 10 dakika içinde %85’ten fazla çözünmüştür. Sonuç: Enalapril maleat ve amlodipin besilatın dozaj formlarından analizinde deney tasarımı faydalı bir yaklaşım olarak görülmüştür. Optimize edilen yöntemin enalapril ve amlodipin içeren bir sabit dozlu kombinasyonun in vitro performansı ve kalite kontrol testlerinde kullanılabileceği gösterilmiştir.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | Sarısaltık Yaşın D, Arslanturk Bıngul A, KARAKUCUK A, Teksin Z (2021). Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. , 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| Chicago | Sarısaltık Yaşın Diren,Arslanturk Bıngul Alev,KARAKUCUK ALPTUG,Teksin Zeynep Şafak Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. (2021): 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| MLA | Sarısaltık Yaşın Diren,Arslanturk Bıngul Alev,KARAKUCUK ALPTUG,Teksin Zeynep Şafak Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. , 2021, ss.66 - 75. 10.4274/tjps.galenos.2020.89725 |
| AMA | Sarısaltık Yaşın D,Arslanturk Bıngul A,KARAKUCUK A,Teksin Z Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. . 2021; 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| Vancouver | Sarısaltık Yaşın D,Arslanturk Bıngul A,KARAKUCUK A,Teksin Z Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. . 2021; 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| IEEE | Sarısaltık Yaşın D,Arslanturk Bıngul A,KARAKUCUK A,Teksin Z "Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination." , ss.66 - 75, 2021. 10.4274/tjps.galenos.2020.89725 |
| ISNAD | Sarısaltık Yaşın, Diren vd. "Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination". (2021), 66-75. https://doi.org/10.4274/tjps.galenos.2020.89725 |
| APA | Sarısaltık Yaşın D, Arslanturk Bıngul A, KARAKUCUK A, Teksin Z (2021). Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. Turkish Journal of Pharmaceutical Sciences, 18(3), 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| Chicago | Sarısaltık Yaşın Diren,Arslanturk Bıngul Alev,KARAKUCUK ALPTUG,Teksin Zeynep Şafak Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. Turkish Journal of Pharmaceutical Sciences 18, no.3 (2021): 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| MLA | Sarısaltık Yaşın Diren,Arslanturk Bıngul Alev,KARAKUCUK ALPTUG,Teksin Zeynep Şafak Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. Turkish Journal of Pharmaceutical Sciences, vol.18, no.3, 2021, ss.66 - 75. 10.4274/tjps.galenos.2020.89725 |
| AMA | Sarısaltık Yaşın D,Arslanturk Bıngul A,KARAKUCUK A,Teksin Z Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. Turkish Journal of Pharmaceutical Sciences. 2021; 18(3): 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| Vancouver | Sarısaltık Yaşın D,Arslanturk Bıngul A,KARAKUCUK A,Teksin Z Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination. Turkish Journal of Pharmaceutical Sciences. 2021; 18(3): 66 - 75. 10.4274/tjps.galenos.2020.89725 |
| IEEE | Sarısaltık Yaşın D,Arslanturk Bıngul A,KARAKUCUK A,Teksin Z "Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination." Turkish Journal of Pharmaceutical Sciences, 18, ss.66 - 75, 2021. 10.4274/tjps.galenos.2020.89725 |
| ISNAD | Sarısaltık Yaşın, Diren vd. "Development and Validation of an HPLC Method Using an Experimental Design for Analysis of Amlodipine Besylate and Enalapril Maleate in a Fixed-dose Combination". Turkish Journal of Pharmaceutical Sciences 18/3 (2021), 66-75. https://doi.org/10.4274/tjps.galenos.2020.89725 |
