Determination of Nateglinide in Tablet Formulation by HPLC Using a Pentafluorophenyl Core-Shell Column

Öz

Nateglinide is an insulin secretagogue which has been used for the treatment of Type 2 Diabetes mellitus. A simple analytical methodology for determination of nateglinide in tablet formulation is described. An isocratic reversed phase high performance liquid chromatographic (HPLC) method was developed using Kinetex pentafluorophenyl (PFP) (5μm particle size and 4.6 x 150 mm id) core-shell column as stationary phase and 0.05 M Na2HPO4 (pH=2.0) / methanol (30:70 v/v) mixture as mobile phase with the flow rate of 1.0 mL min-1 and diode-array detector at 215 nm. Column was termostated at 22°C. Under these conditions nateglinide was eluted with a symmetrical peak shape and the retention time was 4.779 minutes. The system suitability parameters such as tailing factor, capacity factor and theoretical plate were evaluted. The method was validated as per International Council on Harmonisation (ICH) guidelines. Linearity was obtained in the 2.54 - 40.70 μg mL-1 concentration range with equation y= 10.818x + 4.7048 (R2= 0.998). Limit of detection and limit of quantification were 1.07 and 2.54 μg mL-1. Accuracy of the method was tested by recovery studies which were in the range of 98.78 - 100.76 %. The intra-day and inter-day precision studies were carried out and the relative standard deviation values of peak areas were within ICH limits. The proposed method was successfully applied to the determination of nateglinide in tablet dosage form.

Anahtar Kelimeler

• Validation
• HPLC
• Nateglinide
• pentafluorophenyl
• core shell column

Tablet Formülasyonundaki Nateglinid’in Pentaflorofenil Core-Shell (Çekirdek-Kabuk) Kolon Kullanılarak HPLC ile Tayini

Öz

Nateglinid Tip 2 Diabetes mellitus tedavisinde kullanılan bir insülin salgılatıcıdır. Bu çalışmada tablet formülasyonundaki nateglinidin tayini için basit bir analitik yöntem geliştirilmiştir. İzokratik ve ters faz yüksek performanslı sıvı kromatografi (HPLC) yöntemi, sabit faz olarak Kinetex pentaflorofenil (PFP) (5μm partikül boyutu ve 4.6 x 150 mm kolon boyutu) core-shell kolon, hareketli faz olarak 0.05 M Na2HPO4 (pH=2.0) / metanol (30:70 v/v) karışımı 1.0 mL dk-1 akış ve 215 nm’de diod dizi dedektör kullanılarak geliştirilmiştir. Termostat kontrollü kolon sıcaklığı 22°C’dir. Bu koşullar altında nateglinid 4.779 dakika alıkonma zamanı ve simetrik bir pik şekliyle elüe olmuştur. Kuyruklanma faktörü, kapasite faktörü ve teorik plaka sayısı gibi sistem uygunluk parametreleri hesaplanmıştır. Analitik yöntem validasyonunun gerektirdiği testler Uluslararası Uyum Konseyi (ICH) yönergelerine göre yapılmıştır. y= 10.818x + 4.7048 (R2= 0.998) doğru denklemi ile 2.54 – 40.70μg mL-1 konsantrasyon aralığında doğrusallık bulundu. Teşhis sınırı 1.07 ve tayin sınırı 2.54 μg mL-1’dir. Yöntemin doğruluğu geri kazanım çalışması ile belirlendi ve yüzde geri kazanım 98.78 – 100.76 aralığında hesaplandı. Gün içi ve günler arası tekrarlanabilirlik çalışmalarıyla elde edilen pik alanlarının bağıl standart sapma değerleri ICH limitleri iç

Anahtar Kelimeler

• validasyon
• HPLC
• nateglinid
• pentaflorofenil
• core-shell kolon

Kaynakça

1. Ali I, Al-Othman ZA, Nagae N, Gaitonde VD, Dutta KK, 2012. Recent trends in ultra-fast HPLC: New generation superficially porous silica columns. Journal of Separation Science, 35: 3235–3249.
2. Bakir DS, Yalcin G, Cucu AK, 2020. Isolation and Determination of Tocopherols and Tocotrienols from the Seed of Capparis Ovata Grown in Turkey by Reversed-Phase High-Performance Liquid Chromatography. Chromatographia, 83: 77–86.
3. CDER, 1998. Reviewer Guidance - Validation of chromatographic methods. Center for Drug Evaluation and Research.
4. Cui M, Li N, Qin F, Li F, Xiong Z, 2010. Simultaneous determination of 14 illegal adulterants in Chinese proprietary medicines using reversed-phase ion-pair LC. Chromatographia, 72: 1189–1194.
5. Dey S, Basak S, De A, Alam SP, Hossain T, Saha A, Ghosh M, Karmakar T, 2020. Simultaneous Pharmacokinetics Estimation of Nateglinide and Pioglitazone by RP-HPLC: Computational Study to Unlock the Synergism. Journal of Chromatographic Science, 58: 309–322.
6. El-Zaher AA, Elkady EF, Elwy HM, Saleh MAEM, 2018. A new rapid and economic liquid chromatographic method for simultaneous determination of meglitinides with metformin: application in the presence of metformin and repaglinide impurities and related compounds. Journal of the Iranian Chemical Society, 15: 61–74.
7. Frenkel G, Sheva B, Gome B, Lezion R, Wizel S, Tiqva P, 2009. United States Patent. US 7.534,913 B2.
8. Hacıoğlu A, Çıtlak A, Karakuş S, 2015. Nateglinid etken maddesinin miktar tayini için HPLC yönteminin geliştirilmesi ve validasyonu. Marmara Pharmaceutical Journal, 19: 103–108.

9. ICH, 2005. Validation of Analytical Procedure: Text and Methodology Q2 (R1). ICH Steering Comittee.
10. Jain S, Bhandari A, Purohit S, 2009. Spectrophotometric determination of nateglinide in bulk and tablet dosage forms. Asian Journal of Pharmaceutics, 3: 218–221.
11. Lam YH, Leung MT, Ching CK, Mak TWL, 2020. Simultaneous detection of 24 oral antidiabetic drugs and their metabolites in urine by liquid chromatography–tandem mass spectrometry. Journal of Chromatography B, 1141.
12. Madhavi A, Reddy GS, Suryanarayana M V., Naidu A, 2008. Development of a new analytical method for determination of related components in nateglinide. Chromatographia, 67: 639–645.
13. Maggi L, Bruni G, Maietta M, Canobbio A, Cardini A, Conte U, 2013. I. Technological approaches to improve the dissolution behavior of nateglinide, a lipophilic insoluble drug: Nanoparticles and co-mixing. International Journal of Pharmaceutics, 454: 562–567.
14. Sankalia JM, Sankalia MG, Sutariya VB, Mashru RC, 2007. Nateglinide quantification in rabbit plasma by HPLC: Optimization and application to pharmacokinetic study. Journal of Pharmaceutical and Biomedical Analysis, 44: 196–204.
15. Serni E, Venir E, Romano G, Guerra W, Robatscher P, 2020. Determination of Major Phenolics Content in Dried Apples from Three New Cultivars (Malus domestica Borkh.) Using HPLC-UV-FL with Pentafluorophenyl Stationary Phase. Food Analytical Methods, 13: 863–871.
16. Upadhyay J, Polyzos SA, Perakakis N, Thakkar B, Paschou SA, Katsiki N, Underwood P, Park KH, Seufert J, Kang ES, Sternthal E, Karagiannis A, Mantzoros CS, 2018. Pharmacotherapy of type 2 diabetes: An update. Metabolism: Clinical and Experimental, 78: 13–42.
17. Xavier CM, Basavaiah K, Ramesh J, Vinay KB, Revanasiddappa HD, 2012. RP-UPLC Method Development and Validation for the Determination of Nateglinide in Bulk Drug and Pharmaceutical Formulations : A Quality by Design Approach. Malaysian Journal of Pharmaceutical Sciences, 10: 23–44.
18. Yıldırım S, Karakoç HN, Yaşar A, Köksal İ, 2020. Determination of levofloxacin, ciprofloxacin, moxifloxacin and gemifloxacin in urine and plasma by HPLC-FLD-DAD using pentafluorophenyl core-shell column: Application to drug monitoring. Biomedical chromatography : BMC: e4925.