Sci. Pharm. 2009; 77: 579–587
Isolation and Characterization of a Trace Level Unknown Impurity of Salmeterol by Chromatographic and Spectroscopic Methods
Bandaru VENKATASUBBAIAH * 1, Lakki Reddy PRAKASH 1, Rudraraju VASU DEV 2, Vakamudi VARAPRASAD 3, Kalluru SUBRAMANYAM REDDY 4
1 Analytical Research and Development, Integrated Product Development, Dr. Reddy’s Laboratories Ltd., Bachupally, Hyderabad-500 072, India.
2 Analytical Research, Discovery Research, Dr. Reddy’s Laboratories Ltd., Miyapur, Hyderabad-500 049, India.
3 Analytical Research and Development, Integrated Product Development, Dr. Reddy’s Laboratories Ltd., Bachupally, Hyderabad-500 072, India.
4 Department of Chemistry, Sri Venkateswara University, Tirupati-517 502, India.
* Corresponding author. E-mail: venkatasb@drreddys.com (B. Venkatasubbaiah).
Abstract
During the process development of Salmeterol, an unknown impurity was detected at 2.08 Relative Retention Time (RRT) at a level of 0.11% by a gradient Reverse Phase-High Performance Liquid Chromatography (RP-HPLC). The impurity was isolated from the salmeterol drug substance using preparative HPLC. The separation was achieved with an Inertsil C8 column, using acetonitrile–trifluroacetic acid buffer pH 2.7 as mobile phase. The isolated impurity was characterized by NMR and MS techniques. The impurity has been characterized as 4-(2-{[6-(4-cyclohexylbutoxy)hexyl]amino}-1-hydroxyethyl)-2-(hydroxymethyl)phenol. The synthesis of the impurity and its formation was also discussed.
Keywords
Salmeterol Impurity • Preparative HPLC • Spectroscopy • Isolation • Identification and Characterization
Received June 1st, 2009 | Accepted July 2nd, 2009 | Published Online July 4th, 2009
