The Column - January 2008 - (Page 12)

Forsatz and Snow The Column www.thecolumn.eu.com January 2008 HPLC with Charged Aerosol Detection for Pharmaceutical Cleaning Validation Brian Forsatz1,2 and Nicolas H. Snow,1 1Seton Hall University, South Orange, New Jersey, USA, 2Schering-Plough Research Institute, Union, New Jersey, USA. Cleaning validation is a major analytical application in the pharmaceutical industry. Here, high performance liquid chromatography (HPLC) with charged aerosol detection is compared and contrasted to HPLC with Ultraviolet detection. Quantification of a drug substance is demonstrated along with the potential of charged aerosol detection for nonchromophoric excipients. Good manufacturing practice (GMP) requires that equipment involved in manufacturing is cleaned to certain low-level specifications and that assays and detection limits for confirming equipment cleanliness must be improved continuously. Validation of cleaning processes has long played a critical role in pharmaceutical manufacturing. The US Food and Drug Administration (FDA) requires that firms have written procedures detailing the cleaning processes used for various pieces of equipment and procedures for validating them.1 Typical detection limits described in the pharmaceutical literature are 10 ppm of the analyte or a biological activity level of 1/1000 of the normal therapeutic dose.2 Cleaning validation generally involves a separation of the drug substance by high performance liquid chromatography (HPLC) and quantification of the residual material on the manufacturing device based upon a reference standard. HPLC with ultraviolet/visible (UV/vis) detection is used commonly for cleaning validation as well as for traditional assays. HPLC cleaning validation methods are often similar to drug substance assays and in some instances can be the exact same method. Authors: Brian Forsatz and Nicholas H. Snow E-mail: snownich@shu.edu While HPLC with UV/vis detection is an important means for assaying one drug substance, if impurities are present, the response at the assay wavelength for those impurities must be known and might not be as strong as for the drug substance. In addition, any residual material on the equipment that does not have a chromophore will not give a response. By using HPLC with charged aerosol detection, these problems are eliminated. Charged aerosol detection is based upon using an electrical aerosol analyser together with HPLC.3,4 It operates by detecting charged particles that have a selected range of mobility rather than by measuring individual gas-phase ions that are differentiated based upon mass-to-charge ratio (m/z).5 A simplified explanation of how charged aerosol detection acquires a signal from a compound that is being analysed is shown in Figure 1. The mobile phase is nebulized using nitrogen as the carrier gas, followed by the droplets in the aerosol shrinking as the solvent evaporates. This stream of particles from the nebulizer is met with a second stream of positively charged nitrogen gas from a high-voltage platinum corona charger in a mixing chamber, where the positive charge 12 http://www.thecolumn.eu.com

Table of Contents for the Digital Edition of The Column - January 2008

The Column - January 2008
Contents
News
Zosimus
Cover Story: HPLC with Charged Aerosol Detection for Pharmaceutical Cleaning Validation
Market Trends and Analysis
Far From Staying Stationary: Q&A

The Column - January 2008