STRATEGIC QBD IMPLEMENTATION IN RPHPLC-PDA METHOD FOR SIMULTANEOUS QUANTIFICATION OF CYSTIC FIBROSIS DRUGS TEZACAFTOR AND IVACAFTOR

Anusha Gandi; Srinivasa Rao Yarguntla; Varaprasada Rao K

Makale detayları

STRATEGIC QBD IMPLEMENTATION IN RPHPLC-PDA METHOD FOR SIMULTANEOUS QUANTIFICATION OF CYSTIC FIBROSIS DRUGS TEZACAFTOR AND IVACAFTOR

Yazarlar:

Anusha Gandi | Srinivasa Rao Yarguntla | Varaprasada Rao K

Yayıncı:

Ankara University

Ana Başlıklar:

Eczacılıkta Analitik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 2, pp.477-490

Belge Tipi:

Makale

Yayın Tarihi:

5/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347662

pISSN:

1015-3918

Anahtar kelimeler:

Özet:

 Objective: A novel RP-HPLC PDA method was developed using a Quality by Design QbD approach for the simultaneous quantification of Tezacaftor and Ivacaftor medications employed in the management of cystic fibrosis. Material and Method: Optimization was performed by Central Composite Design by selecting mobile phase ratio of methanol, pH of buffer and flow rate as factors and evaluating responses namely retention time and tailing factor. This technique makes use of an Inertial ODS C18 column 250 x 4.6 mm, 5 μm particle size in conjunction with a Waters module fitted with a photo diode array detector. The chromatographic conditions including a flow rate of 1.0 mlmin, a mobile phase composed of methanol and buffer in a 45:55 ratio, and a detection wavelength of 210 nm, were thoughtfully designed to effectively separate Tezacaftor and Ivacaftor. Result and Discussion: The method demonstrated remarkable accuracy, with average recoveries of 99.69 for ivacaftor and 100.06 for tezacaftor. The  assay results for system suitability, method precision, and intermediate precision consistently fell within the range of 99.91 to 100.37. Linearity data exhibited correlation coefficient values of one for both Tezacaftor and Ivacaftor. The LOD and LOQ values for Tezacaftor and Ivacaftor were determined to be 0.56, 0.57, 1.69, and 1.74, respectively. The results obtained from the validation parameters demonstrate that this RP-HPLC method, developed using the QbD approach, is robust and dependable. It serves as a valuable tool for routine analysis and plays a pivotal role in bioanalytical and bioequivalence research within the realm of cystic fibrosis treatment. This method ensures precise and accurate quantification of Tezacaftor and Ivacaftor in combination tablet formulations.

 Objective: A novel RP-HPLC PDA method was developed using a Quality by Design QbD approach for the simultaneous quantification of Tezacaftor and Ivacaftor medications employed in the management of cystic fibrosis. Material and Method: Optimization was performed by Central Composite Design by selecting mobile phase ratio of methanol, pH of buffer and flow rate as factors and evaluating responses namely retention time and tailing factor. This technique makes use of an Inertial ODS C18 column 250 x 4.6 mm, 5 μm particle size in conjunction with a Waters module fitted with a photo diode array detector. The chromatographic conditions including a flow rate of 1.0 mlmin, a mobile phase composed of methanol and buffer in a 45:55 ratio, and a detection wavelength of 210 nm, were thoughtfully designed to effectively separate Tezacaftor and Ivacaftor. Result and Discussion: The method demonstrated remarkable accuracy, with average recoveries of 99.69 for ivacaftor and 100.06 for tezacaftor. The  assay results for system suitability, method precision, and intermediate precision consistently fell within the range of 99.91 to 100.37. Linearity data exhibited correlation coefficient values of one for both Tezacaftor and Ivacaftor. The LOD and LOQ values for Tezacaftor and Ivacaftor were determined to be 0.56, 0.57, 1.69, and 1.74, respectively. The results obtained from the validation parameters demonstrate that this RP-HPLC method, developed using the QbD approach, is robust and dependable. It serves as a valuable tool for routine analysis and plays a pivotal role in bioanalytical and bioequivalence research within the realm of cystic fibrosis treatment. This method ensures precise and accurate quantification of Tezacaftor and Ivacaftor in combination tablet formulations.

 Objective: A novel RP-HPLC PDA method was developed using a Quality by Design QbD approach for the simultaneous quantification of Tezacaftor and Ivacaftor medications employed in the management of cystic fibrosis. Material and Method: Optimization was performed by Central Composite Design by selecting mobile phase ratio of methanol, pH of buffer and flow rate as factors and evaluating responses namely retention time and tailing factor. This technique makes use of an Inertial ODS C18 column 250 x 4.6 mm, 5 μm particle size in conjunction with a Waters module fitted with a photo diode array detector. The chromatographic conditions including a flow rate of 1.0 mlmin, a mobile phase composed of methanol and buffer in a 45:55 ratio, and a detection wavelength of 210 nm, were thoughtfully designed to effectively separate Tezacaftor and Ivacaftor. Result and Discussion: The method demonstrated remarkable accuracy, with average recoveries of 99.69 for ivacaftor and 100.06 for tezacaftor. The  assay results for system suitability, method precision, and intermediate precision consistently fell within the range of 99.91 to 100.37. Linearity data exhibited correlation coefficient values of one for both Tezacaftor and Ivacaftor. The LOD and LOQ values for Tezacaftor and Ivacaftor were determined to be 0.56, 0.57, 1.69, and 1.74, respectively. The results obtained from the validation parameters demonstrate that this RP-HPLC method, developed using the QbD approach, is robust and dependable. It serves as a valuable tool for routine analysis and plays a pivotal role in bioanalytical and bioequivalence research within the realm of cystic fibrosis treatment. This method ensures precise and accurate quantification of Tezacaftor and Ivacaftor in combination tablet formulations.

 Amaç: Kistik fibrozis tedavisinde kullanılan Tezacaftor ve Ivacaftor ilaçlarının eş zamanlı ölçümü için Tasarıma Göre Kalite QbD yaklaşımı kullanılarak yeni bir RP-HPLC PDA yöntemi geliştirildi. Gereç ve Yöntem: Optimizasyon, metanolün mobil faz oranı, tamponun pHı ve akış hızının faktör olarak seçilmesi ve tepkilerin, yani alıkonma süresi ve kuyruk faktörünün değerlendirilmesi yoluyla Merkezi Bileşik Tasarım ile gerçekleştirildi. Bu teknik, bir foto diyot dizisi dedektörü ile donatılmış bir Waters modülü ile birlikte bir Inertial ODS C18 kolonundan 250 x 4,6 mm, 5 μm parçacık boyutunda yararlanır. 1.0 mldaklık bir akış hızı, 45:55 oranında metanol ve tampondan oluşan bir mobil faz ve 210 nmlik bir tespit dalga boyunu içeren kromatografik koşullar, Tezacaftor ve Ivacaftoru etkili bir şekilde ayırmak için iyi bir şekilde tasarlanmıştır. Sonuç ve Tartışma: Yöntem, ivacaftor için 99.69 ve tezacaftor için 100.06lık ortalama geri kazanımlarla dikkate değer bir doğruluk gösterdi. Sistem uygunluğu, yöntem kesinliği ve ara kesinlik için  miktar tayini sonuçları sürekli olarak 99.91 ile 100.37 aralığında tespit edildi. Doğrusallık verileri, hem Tezacaftor hem de Ivacaftor için bir korelasyon katsayısı değeri gösterdi. Tezacaftor ve Ivacaftor için LOD ve LOQ değerleri sırasıyla 0.56, 0.57, 1.69 ve 1.74 olarak belirlendi. Doğrulama parametrelerinden elde edilen sonuçlar, QbD yaklaşımı kullanılarak geliştirilen bu RP-HPLC yönteminin sağlam ve güvenilir olduğunu göstermektedir. Rutin analizler için bu teknik değerli bir araç olarak hizmet eder ve kistik fibroz tedavisi alanında biyoanalitik ve biyoeşdeğerlik araştırmalarında önemli bir rol oynar. Bu yöntem, kombinasyon tablet formülasyonlarında Tezacaftor ve Ivacaftorun kesin ve doğru miktarının belirlenmesini sağlar.

Makale detayları

STRATEGIC QBD IMPLEMENTATION IN RPHPLC-PDA METHOD FOR SIMULTANEOUS QUANTIFICATION OF CYSTIC FIBROSIS DRUGS TEZACAFTOR AND IVACAFTOR

Yazarlar:

Anusha Gandi | Srinivasa Rao Yarguntla | Varaprasada Rao K

Yayıncı:

Ankara University

Ana Başlıklar:

Eczacılıkta Analitik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 2, pp.477-490

Belge Tipi:

Makale

Yayın Tarihi:

5/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347662

pISSN:

1015-3918

Central composite design

ivacaftor

method development

method validation

RP-HPLC

tezacaftorMerkezi kompozit tasarım

ivacaftor

RP-HPLC

tezacaftor

yöntem geliştirme

yöntem validasyonu

Sayı

Makale detayları

Yazarlar: Anusha Gandi | Srinivasa Rao Yarguntla | Varaprasada Rao K

Yayıncı: Ankara University

Ana Başlıklar: Eczacılıkta Analitik Kimya

Dergi: Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 2, pp.477-490

Belge Tipi: Makale

Yayın Tarihi: 5/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001347662

pISSN: 1015-3918

Sayı

Yazarlar:

Anusha Gandi | Srinivasa Rao Yarguntla | Varaprasada Rao K

Yayıncı:

Ankara University

Ana Başlıklar:

Eczacılıkta Analitik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 2, pp.477-490

Belge Tipi:

Makale

Yayın Tarihi:

5/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347662

pISSN:

1015-3918