title: Determination of inorganic pharmaceutical counterions using hydrophilic interaction chromatography coupled with a Corona CAD detector.
abstract: A simple generic approach was investigated for the determination of inorganic pharmaceutical counterions in drug substances using conventional high performance liquid chromatographic (HPLC) instruments. An intuitive approach combined Corona charged aerosol detection (CAD) with a polymer-based zwitterionic stationary phase in the hydrophilic interaction chromatography (HILIC) mode. Two generic methods based on this HILIC/CAD technique were developed to quantitate counterions such as Cl-, Br-, SO(4)(2-), K+, Ca2+ and Mg2+ in different pharmaceutical compounds. The development and capability of this HILIC/CAD technique analysis were examined. HILIC/CAD was compared to ion chromatography (IC), the most commonly used methodology for pharmaceutical counterion analysis. HILIC/CAD was found to have significant advantages in terms of: (1) being able to quantitate both anions and cations simultaneously without a need to change column/eluent or detection mode; (2) imposing much less restriction on the allowable organic percentage of the eluents than IC, and therefore being more appropriate for analysis of counterions of poorly water-soluble drugs; (3) requiring minimal training of the operating analysts. The precision and accuracy of counterion analysis using HILIC/CAD was not compromised. A typical precision of <2.0% was observed for all tested inorganic counterions; the determinations were within 2.0% relative to the theoretical counterion amount in the drug substance. Additionally, better accuracy was shown for Cl- in several drug substances as compared to IC. The main drawback of HILIC/CAD is its unsuitability for many of the current silica-based HILIC columns, because slight dissolution of silica leads to high baseline noise in the CAD detector. As a result of the universal detection characteristics of Corona CAD and the unique separation capabilities of a zwitterionic stationary phase, an intuitive and robust HPLC method was developed for the generic determination of various counterions in different drug substances. HILIC/CAD technique is a useful alternative methodology, particularly for determination of counterions in low-solubility drugs.
authors.affiliation: Bristol-Myers Squibb, Research and Development, 1 Squibb Drive, New Brunswick, NJ 08901, USA. zongyun.huang@bms.com
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: M A
authors.initials: MA
authors.lastname: Richards
authors.forename: Y
authors.initials: Y
authors.lastname: Zha
authors.forename: R
authors.initials: R
authors.lastname: Francis
authors.forename: R
authors.initials: R
authors.lastname: Lozano
authors.forename: J
authors.initials: J
authors.lastname: Ruan
mesh_terms: D000336:Aerosols; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002845:Chromatography / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002852:Chromatography, Ion Exchange / Q000379:methods; D004867:Equipment Design; D005740:Gases; D007477:Ions; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
chemical_list: D000336:Aerosols; D005740:Gases; D007477:Ions; D004364:Pharmaceutical Preparations; D012822:Silicon Dioxide