Bristol-Myers Squibb, Research and Development, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
J Pharm Biomed Anal. 2009 Dec 5;50(5):809-14. doi: 10.1016/j.jpba.2009.06.039. Epub 2009 Jun 27.
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.
本研究旨在考察一种通用的方法，以利用常规高效液相色谱（HPLC）仪器测定药物中的无机药物抗衡离子。该方法将直观的 Corona 荷电气溶胶检测（CAD）与亲水相互作用色谱（HILIC）模式下的聚合物两性离子固定相相结合。基于该 HILIC/CAD 技术建立了两种通用方法，用于定量测定不同药物中的抗衡离子，如 Cl-、Br-、SO4(2-)、K+、Ca2+和 Mg2+。考察了该 HILIC/CAD 技术分析的开发和能力。将 HILIC/CAD 与离子色谱（IC）进行了比较，后者是用于药物抗衡离子分析的最常用方法。结果表明，HILIC/CAD 具有以下显著优势：（1）无需改变柱/洗脱液或检测模式即可同时定量测定阴离子和阳离子；（2）与 IC 相比，对洗脱液允许的有机百分比的限制要小得多，因此更适合分析水溶性差的药物的抗衡离子；（3）对操作人员的培训要求较低。HILIC/CAD 用于抗衡离子分析的精密度和准确性并未受到影响。所有测试的无机抗衡离子的典型精密度均<2.0%；相对于药物中理论抗衡离子的量，测定值在 2.0%以内。此外，与 IC 相比，几种药物中的 Cl- 表现出更好的准确性。HILIC/CAD 的主要缺点是不适合许多当前的基于硅胶的 HILIC 柱，因为硅胶的轻微溶解会导致 CAD 检测器中的基线噪声很高。由于 Corona CAD 的通用检测特性和两性离子固定相的独特分离能力，开发了一种直观而稳健的 HPLC 方法，用于不同药物中各种抗衡离子的通用测定。HILIC/CAD 技术是一种有用的替代方法，特别是用于测定低溶解度药物中的抗衡离子。
