Chiral Separation of Carboprost Isomers by Normal Phase LC Using Amylose Chiral Stationary Phase

LC separation of carboprost diastereomers in bulk drug was developed and validated using normal-phase amylose stationary phase Chiralpak AD-H. The effect of the organic modifiers, namely 2-propanol and ethanol in the mobile phase was optimized in order to obtain the best separation. The retention time of (R)-carboprost and (S)-carboprost were 15.3 and 17.1 min, respectively. Calibration curves were linear over the range of 0.2–1.0%, with the regression coefficient (R ²) of 0.9997. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.07 and 0.2%, respectively. The method was accurate, precise and suitable to use for the purpose of controlling unwanted (R)-isomer in the carboprost active pharmaceutical ingredient. This method can be successfully applied to the analysis of chiral purity of carboprost in pharmaceutical bulk drug samples.     

Unusual detritylation of tritylated tetrazole in Sartan molecules

Tritylated tetrazole of 2a underwent unusual detritylation under basic reaction condition during the synthesis of methyl ether of olmesartan medoxomil 1. The unusual detritylation was found to be a common feature in the case of all tetrazole containing Sartan molecules (3-7).     

A convenient and practical synthesis of olmesartan medoxomil methyl ether

Synthesis of Olmesartan medoxomil methyl ether ( 2 ), a potential impurity of Olmesartan medoxomil ( 1 ), an angiotensin II receptor blockers is reported for the first time.