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Streamlining System Suitability Evaluations for USP Methods

Terry Rankin Jessie Butler Fausto Pigozzo Sorin Trestianu


ThermoQuest CE Instruments, 2215 Grand Avenue Pkwy, Austin, Texas 78728-3812

Introduction

USP has established protocol for testing the quality of data generated by analytical instruments. The standards are listed in each
monograph under system suitability. Operating under strict guidelines governing procedures and quality control, the pharma-
ceutical lab has incorporated computers to facilitate the evaluation of data. Most of these computers require that the operator have
some knowledge of writing macros for generation of post run calculations for the testing of USP criteria1. The ChromQuest
Software Data System has been developed to streamline not only instrument control but also compilation of data and quality
control (QC) summary reports. ChromQuest does this by featuring standard exporting and automatic performance calculations
after acquisition. The software makes post run decisions based on the limits entered by the operator. If a sample fails the USP
protocol, it may be reinjected or the run scheme may be paused. The software controls all instrumentation in the lab including gas
chromatographs (GC), high pressure liquid chromatographs (HPLC), and capillary electrophoresis (CE) instrumentation. The
ChromQuest™ Software Data System is more than a software package for instrument control and data processing; it is a QC
reviewer with the ability to make post run decisions for results that fall outside of the limits set by the lab manager.

System Suitability

System suitability is an important test for the quality of data obtained in gas and liquid chromatography. It is a good indicator of
the whole analytical process including methods and standards. The information obtained for performance of a system is not only
helpful for method development but also during day to day operation. Initially, resolving the peaks of interest for the prescribed
column is investigated. If the peaks have good resolution, each peak's symmetry should be examined, particularly if the polarity
of the analytes and the column are dissimilar. Optimizing peak shape is essential since injecting dirty samples will usually degrade
performance over time. As defined in the USP manual, for two components in a mixture, the resolution, R, is determined by the
equation:
2 (t2 - t1)
R=
W2 + W1
in which t2 and t1 are the retention times of the two components, and W1 and W2 are the corresponding widths at bases of the peaks
of interest2. The peak asymmetry is judged by the tailing factor T, as is determined by the equation:
W0.05
T=
2f
where W0. 05 is peak width at 5% height and f is the distance from the peak maximum to the leading edge of the peak, the distance
being measured at a point 5% of the peak height from the baseline. Calculation of system suitability is done automatically by
entering the following instrument parameters: the unretained peak time and column length. In the set up screen the performance
parameters to be tested are selected for each analyte, Figure 1.

Resolution, reproducibility and precision are important QC parameters to track. The analytical batch can be used to test system
suitability precision as will be shown later. The suitable precision is tested for using the standard statistical Percent Relative
Standard Deviation.

For those analyses with only one peak, column efficiency and tailing can be especially helpful and needed. For Gaussian peaks:
2

N = 16 or N = 5.54 ( (
1
W1/2
where N is the number of theoretical plates, t is the retention time of the substance, and W1/2 is the peak width at half height. The
number of theoretical plates is a good judge of column efficiency. When only a single peak is obtained, N gives some assurance
against coeluting peaks disrupting the analysis. Since choice of column phases usually are mandated but not the dimensions, the
analyst is given much leeway on setting up an analysis. While phase is the most important determinant of N, the analyst should
definitely examine all parameters in conjunction with N to optimize the analysis. For instance capacity of narrow bore (<0.18
mm) columns is much less than Megabore (>0.53 mm), resulting in high analyte concentrations degrading performance
substantially.

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Figure 1. Selection system suitability USP performance tests

ChromQuest gives the user added flexibility in the measurement of column performance. These factors can be calculated by
different equations as spelled out by various regulatory and trade groups worldwide. USP recognizes that the procedures
specified in a monograph may not apply to some situations and suggests the use of more applicable methods (as stated in
Procedures under Tests and Assays in General Notices1). ChromQuest gives users the option of using EMG (Exponential
Modified Gaussian) methods favored by some or the methods preferred by DAB (German Pharmacopoeia), JP (Japanese
Pharmacopoeia), BP (British Pharmacopoeia), EP (European Pharmacopoeia) or ASTM.

For those who need to calculate special or unique parameters ChromQuest gives them many options. There are some programs
which are already written for this, but for those who wish to write their own, a .DLL can be written. ChromQuest gives full access
of data to be passed to these programs. These custom parameters are available for use in many parts of ChromQuest. In addition
ChromQuest can launch other programs from different sections of the software to perform whatever actions or functions the user
desires.

A Chromatography System Validation Package includes the SS120C Chromatogram Generator, the Virtual Peak Generator
software, and a Chromatogram Testing Kit. This package provides the tools you need for the validation of your chromatography
data system. Some of the instrumental tests that can be done are noise and drift. The signal generator simulates a perfect GC or
HPLC analog signal to evaluate the performance of electronic components unique to the data system. These tests are necessary
for data system certification.

All of the parameters mentioned above can be reported, exported to other programs, used for instrument control options,
controlling the execution of other programs, and many other features. Reporting of these values is easy.

Reporting Data

Getting data into a useful format is critical to productivity in the laboratory. ChromQuest features a customized report editor. You
may modify existing reports or create your own. ChromQuest allows any information to be contained in a predesigned report as
shown in Figure 2. ChromQuest permits the creation of reports using data, customized data, methods, sequences, custom
parameters, and many other choices. In addition ChromQuest allows Objects to be inserted into reports. These can be simple
bitmaps, graphs, and spreadsheets to any objects supported by OLE such as audio or video clips. Creating reports is easy because
the report editor is graphics intensive.

An example used here is looking for Organic Volatile Impurities (OVIs) in pharmaceuticals 3. USP methods ordinarily stipulate
that resolution not be less than 3 with a precision not more than 15%. Five replicates are run as specified in the monograph for
each substance or product to test for system suitability. A typical real time chromatogram of the five OVIs in USP Method 467 is
shown in Figure 3. Reports can be constructed in any form desired; inserting fields, graphs, etc. any way desired. Custom
parameters can also be put in reports. A suitability report is shown in Figure 4. Data can be exported to other programs for
analysis and reporting.

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Figure 2. Custom reporting with various options

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Figure 3. Typical real time display of OVIs

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Figure 4. System suitability summary report

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Export Options
For those who wish to export their data, ChromQuest gives the user many options. Individual parameters may be selected and
exported to a spreadsheet for tabulation. These files are formatted for Microsoft Excel or other Windows applications. The files
can also be exported in AIA format for use by third party programs. Standard and performance reports may be exported readily as
shown in Figure 5. Not only can performance criteria be used for reporting or exporting to other software, it can be used to control
the execution of batch sequences on the instrument.

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Figure 5. Exporting for generation of ASCII files by simply specifying a path and selecting parameters

Instrument Control

ChromQuest batch sequences do more than run a batch of samples. They can produce and examine all kinds of QC information.
In the sequence the operator simply flags the sample's type as shown in Figure 6 under Sample Run Type. ChromQuest
automatically generates the appropriate reports, and then controls sequence executions and other features. To control the sequence
the user will need to decide what actions to take under the different conditions chosen to examine for controlling the sequence and
enhancing sample throughput, Figure 7. There are also options to communicate with other programs. The operator may even be
paged when certain conditions occur.

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Figure 6. Flagging sample types

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Figure 7. The software preforms post run instrument control


enhancing sample throughput

Conclusion

The pharmaceutical lab is achieving higher sample throughput with smarter software packages like ChromQuest. System
suitability is automatically tested and post run decisions made based on operator specified limits. The ChromQuest Software Data
System controls instrumentation, acquires data, generates quantitation reports, calculates system suitability performance criteria,
exports information, and alters the batch sequence for unattended operation. A Chromatogram System Validation Package is
available with a virtual peak generator for testing hardware prior to the analysis of the samples. Customized software saves the
production lab operator time, reducing the cost of the analysis.

References
1
USP 23-NF 18, United States Pharmacopeial Convention, Inc., January 1995
2
USP 23-NF 18, Method 621 Chromatography, System Suitability, 1775-1777
3
USP 23-NF 18, Method 467, Organic Volatile Impurities, 1746-1748

CE INSTRUMENTS
Copyright 1998 by CE Instruments, a subsidary of ThermoQuest Corporation. All rights reserved. Printed in the United States of America.

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