Pharmaceutical industry has been emerging rapidly for the last decade by focusing on product Quality, Safety, and Efficacy. Pharmaceutical firms increased the number of product development by using scientific tools such as QbD (Quality by Design) and PAT (Process Analytical Technology). ICH guidelines Q8 to Q11 have discussed QbD implementation in API synthetic process and formulation development. ICH Q11 guidelines clearly discussed QbD approach for API synthesis with examples. Generic companies are implementing QbD approach in formulation development and even it is mandatory for USFDA perspective. As of now there is no specific requirements for AQbD (Analytical Quality by Design) and PAT in analytical development from all regulatory agencies. In this review, authors have discussed the implementation of QbD and AQbD simultaneously for API synthetic process and analytical methods development. AQbD key tools are identification of ATP (Analytical Target Profile), CQA (Critical Quality Attributes) with risk assessment, Method Optimization and Development with DoE, MODR (method operable design region), Control Strategy, AQbD Method Validation, and Continuous Method Monitoring (CMM). Simultaneous implementation of QbD activities in synthetic and analytical development will provide the highest quality product by minimizing the risks and even it is very good input for PAT approach.

Objective: The objective of the present study is to develop a stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for qualitative and quantitative determination of Eptifibatide and its impurities in bulk and pharmaceutical dosage forms. Methods: The chromatographic separation was carried on Phenomenex Luna C18 column (250 mm×4.6 mm; 5µ id) as stationary phase, methanol and phosphate buffer at pH 6.4 in the ratio of 65:45 (v/v) as mobile phase at flow rate of 1.0 ml/min, Ultra Violet (UV) detection was carried at the wavelength of 236 nm and the analysis was completed with a run time of 15 min. Results: In the developed conditions, the retention time of Eptifibatide and its impurities 1 and 2 were found to be 3.35, 4.93 and 8.18 min, respectively. The method was validated for system suitability, range of analysis, precision, specificity, stability and robustness. Spiked recovery at 50%, 100% and 150% was carried for both standard and impurities and the acceptable % recovery of 98-102 was observed for Eptifibatide and both impurities studied and the % Relative standard deviation (RSD) in each spiked level was found to be less than 2. Stability tests were done through the exposure of the analyte solution to five different stress conditions i. e expose to 1N Hydrochloric acid (HCl), 1 N Sodium hydroxide (NaOH), 3% Hydrogen peroxide (H2O2), 80 °C temperature to UV radiation. In all the degradation conditions, standard drug Eptifibatide was detected along with both the impurities studied and the degradation products were successfully separated. In the formulation analysis, there is no other chromatographic detection of other impurities and formulation excipients. Conclusion: The developed method was found to be suitable for the quantification of Eptifibatide and can separate and analyse impurities 1 and 2.

A novel high speed, high resolution Reverse phase-UPLC method was developed for the quantification of related substances in Febuxostat drug substance. The separation of drug from the possible impurities was achieved on a Halo C18 column. The innovative approach of using stationary phase with sub 2 µ particles provides a comprehensive combination of selectivity and speed. 10 mM mono basic potassium phosphate buffer at pH 2.7 and acetonitrile mixture was selected as mobile phase. Flow rate and detection were kept at 0.8 mL/min and 320 nm respectively. The developed UPLC method was subjected to validation parameters. System precision, accuracy, specificity, limit of detection, limit of quantification and linearity were established as per the guidelines recommended by ICH. Stability indicating nature of the method was also performed by exposing the sample under various conditions like acid, base, peroxide and photo stability exposures. Total analysis run time 7.0 minutes indicates the speed and cost saving initiation of the developed method. Using the method one can carry out the quantitative estimation of related substances in Febuxostat drug substance, further the same method can be adopted for determination of drug substance assay also.

A rapid HPLC bio-analytical method has been developed and validated for the simultaneous quantification of Ombitasvir (OMBTSR), Ritonavir (RTNVR), Paritaprevir (PTVR) in human plasma. OMBTSR and PTVR are used to control Hepatitis-C infection. RTNVR is used in the treatment of HIV/AIDS. The method was developed with Column (Intersil ODSC 18, 250 mm × 4.6 mm × 5µ) at 230 nm wave length and at flow rate of 1.0 mL/min. The mobile phase consisted of 20% Acetonitrile, 20% Methanol, 60% 1mM NH 4 H 2 PO 4 Buffer(P H 6.5 v/v). The retention times of RTNVR, OMBTSR, PTVR are 5.7 min. 7.8 min. and 12.8 min. respectively. The method was developed and validated in terms of linearity, interday precision, intraday precision, accuracy, LOQ, LOD and stability study. The proposed method is useful in pharmacokinetic studies using HPLC or LC-MS.

Leflunomid (LFNM), izoksazol türevine ait ve immüne süpresif ve antienflamatuvar aktiviteye sahip bir ilaçtır. Literatür taraması, farmasötik dozaj formlarında ve bulk ilaçlarda LFNM ve ilgili safsızlık A ve B'nin değerlendirilmesi için rapor edilen bir yöntemin olmadığını doğrulamaktadır. Bu nedenle bu çalışma, LFNM'nin ve A ve B safsızlıklarının ayrıştırılması ve miktarının belirlenmesi için hızlı stabilite göstergeli RP-YBSK yöntemini geliştirmeyi amaçlamıştır. Gereç ve Yöntemler: LFNM ve ilgili safsızlık A ve B'nin eş zamanlı analizi için mobil faz oranı, pH, akış hızı, stasyoner faz ve detector dalga boyu gibi metod koşullarının sistematik testleri gerçekleştirilmiştir. Geliştirilen yöntem farklı stress koşullarında zoraki bozunma çalışmalarını içeren ICH yönergelerine göre valide edilmiştir. Bulgular: Optimal ayrıştırma, Thermo Scientific Hypersil ODS C18 kolonu (250 mm×4,6 mm; 5 µm id) üzerinde, 40:30:30 (h/h) oranında asetonitril, methanol ve 0,1 M sodium perklorat bileşiminden oluşan mobil faz kullanılarak elde edilmiştir; izokratik elüsyonda 1,0 mL/dak akış hızında pH 4,6 idi. UV saptaması 246 nm dalga boyunda gerçekleştirilmiştir. İyi-kararlı pikler, çok sayıda teorik plaka, daha az kuyruklama faktörü ve tekrarlanabilir göreceli retansiyon süresi ve tepki faktörü ile elde edilmiştir. Yöntem valide edilmiştir ve tüm validasyon parametreleri kabul limitinde bulunmuştur. Stabilite testleri, analit çözeltisinin beş farklı stress koşuluna, yani 1 N HCl, 1 N NaOH, %3 H 2 O 2 , tozun termal degradasyonuna ve UV radyasyonuna Objectives: Leflunomide (LFNM) is a drug that belongs to isoxazole derivatives and has immunosuppressive and anti-inflammatory activities. A literature search confirms that there is no method reported for the simultaneous estimation of LFNM and its related impurities A and B in pharmaceutical dosage forms or in bulk drug. Hence the present work aimed to develop a simple stability indicating RP-HPLC method for the separation and quantification of LFNM and its impurities A and B. Materials and Methods: Systematic trials of method conditions like mobile phase ratio, pH, flow rate, stationary phase, and detector wavelength were performed for the simultaneous analysis of LFNM and its related impurities A and B. The developed method was validated as per the ICH guidelines including forced degradation studies in different stress conditions. Results: Optimized separation was achieved on a Thermo Scientific Hypersil ODS C18 column (250 mm×4.6 mm; 5 µm id) using mobile phase composition of acetonitrile, methanol, and 0.1 M sodium perchlorate in the ratio of 40:30:30 (v/v), pH 4.6, at a flow rate of 1.0 mL/min in isocratic elution. UV detection was carried out at a wavelength of 246 nm. Well-resolved peaks were observed with high numbers of theoretical plates, lower tailing factor, and reproducible relative retention time and response factor. The method was validated and all the validation parameters were found to be within the acceptance limits. Stability tests were done through exposure of the anal...