Abstract
Octahydro-1H-indole-2-carboxylic acid is a key starting material for the synthesis of Perindopril and Trandolapril. A rapid, economical, simple, sensitive and reliable stability-indicating reverse phase HPLC method developed and validated for the quantitative determination of all isomers related to Octahydro-1H-indole-2-carboxylic acid and its related substances. The compound is non chromophoric, it has three chiral centers and there is a possibility of four pairs of enantiomers. Refractive index detector was used for the quantification of all its isomers. Optimized mobile phase is 10 mM potassium phosphate buffer with pH-3.0. The C18 column (Inertsil ODS-4, 250 mm×4.6 mm×5 μm) is used as the stationary phase with a mobile phase flow rate of 1.5 mLmin–1 and column temperature maintained at 35°C. The developed method was validated as per ICH guidelines for Accuracy, linearity, range, precision, ruggedness, robustness, solution stability, limit of quantification, and limit of detection. A linear range from LOQ to 150% performed for the analyte and its three isomers. The correlation coefficient obtained for all the isomers was more than 0.999. The recoveries obtained for all isomers were found in between 93.9% and 107.9%. The detection limit for all the isomers were about 0.006 mg/mL and the quantification limits were in between 0.022 mg/mL to 0.024 mg/mL respectively. The proposed method can be successfully applied for the quantification of the three isomers in Octahydro-1H-indole-2-carboxylic acid and provides a simple and cost effective quality control tool for routine analysis.
Highlights
Perindopril erbumine (Figure 1) [1], compound with tertbutylamine (1:1) belongs to a group called angiotensin converting enzyme (ACE) inhibitors
ACE inhibitors and perindopril were primarily considered as antihypertensive drugs able to reduce, significantly high blood pressure in hypertensives
EUROPA [3] was the largest study conducted with an ACE inhibitor for secondary prevention of stable coronary artery disease (CAD)
Summary
Perindopril erbumine (Figure 1) [1], compound with tertbutylamine (1:1) belongs to a group called angiotensin converting enzyme (ACE) inhibitors. Using reverse phase HPLC with refractive index detector, raw material and its three isomers were separated, in which (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acid is a key starting material for the synthesis of Perindopril. This methodology was developed and recommended for the determination of amino acid mixtures by Milipore Corporation Waters [22], but was never used for octahydro-IH-indole-2-carboxylic acids This literature explains only about two diastereomers of Trandolapril Raw material but not discussed remaining two diastereomers. The objective of the current study was to develop a stabilityindicating reverse phase HPLC method for the quantitative determination of all isomers related to Octahydro-1H-indole-2carboxylic acid and its related substances. The stock solutions of (2S,3aS,7aS)-Octahydro-1H-indole-2carboxylic acid and the remaining three diastereomers were prepared by dissolving 25 mg of each isomer in 10 mL of mobile phase separately (50%). HPLC column separated isomers were quantified by Refractive index detector (RID)
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