HPLC System Maintenance

Maintain and calibrate the HPLC system periodically. Preventive maintenance performed by a service engineer annually and system calibrations performed every 6 months are recommended. ... 

Most HPLC systems in pharmaceutical laboratories are calibrated every 6-12 months. Periods longer than 12 months are not recommended while periods shorter than 3 months are deemed unnecessary because each HPLC system is also subjected to a daily system suitability check to ensure sufficiency for the application. Ideally, the frequency of calibration should be dictated by the historical data of calibration failures and the manufacturer s recommendation. In practice, 6 months appears to be the norm adopted by most laboratories. Calibration is also required after annual preventive maintenance or major repairs though only the affected modules, and not the entire system, need to be recalibrated. 

The change control SOP warrants particular attention. This procedure should clearly spell out how any deviations in instrument operation/per-formance, and hardware/firmware/software updates are to be handled and documented. It should also make clear what distinguishes routine maintenance, minor vs. major changes and what the procedural differences should be. The change control procedure may be a specific SOP, as part of an HPLC system s validation plan, or as part of the corporate validation master plan (VMP) that is established within each company. 

Referring to the maintenance and troubleshooting sections of an instrument s manual is highly recommended. Many individuals consult manuals only after a catastrophic failure and then only when all other problem-solving approaches have been exhausted. Modern HPLC systems often have self-diagnostic capabilities that help isolate the problem area within the instrument. 

Practical HPLC Methodology and Applications Practical HPLC Method development (Both the last ones are suitable for careful study of a method development and optimization.) Troubleshooting HPLC Systems, a Bench Manual (general hints, maintenance and troubleshooting of the HPLC equipment). 

A tool kit composed of spanners, screwdrivers, etc. designed for HPLC systems is a useful addition to your laboratory. This can usually be purchased from the HPLC manufacturer or may even be supplied with the system. It will contain all of the necessary tools to allow you to undertake routine preventative maintenance (discussed next). If a tool kit does not come with the system, most of the spanners and screwdrivers can be purchased from your local hardware store. It is recommended that you keep a tool kit handy. 

Other important detector types are fluorescence detector (FL), light scattering detector (LS), and the refractive index detector (RI). The FL detection offers the higher sensitivity and the lower detection limits. Nevertheless, these properties are frequently counteracted by the limited number of compounds with native FL therefore, additional derivatization reactions of analytes are usually needed, and the cost of acquisition and maintenance. In addition, when FL is used in HPLC systems, the linear dynamic range is often small for many analytes (even when the dynamic range is relatively large) and care should be taken... 

There is no doubt that electrochemical detectors are more prone to operational diflhcul-ties than most other HPLC detectors, and it is also more difficult to take the corrective action. The close inter-relationship between the chromatograph and the detector makes fault diagnosis and correction even more difficult. A good understanding of the basic principles underlying ED is essential to a logical and hopefully successful approach to system maintenance. Nevertheless some problems associated with ED can be difficult to resolve even for the most experienced workers. 

I have attempted to address these needs in two other texts— through method review and summary in The HPLC Solvent Guide, 2nd edition, and through description of the use and maintenance of LCs in Troubleshooting HPLC Systems A Bench Manual. 

Instrumental developments (e.g., of sector field instruments with multiple ion collection, introduced in 1992, or the insertion of collision and reaction cells in order to reduce disturbing isobaric interferences), the progress in applications for ultratrace analysis, also in combination with on line hyphenated separation techniques (HPLC, CE), especially routine capability as well as decreasing price and user friendly maintenance mean that sales are increasing by 10 % every year. To improve the analytical performance of ICP mass spectrometers for precise isotope ratio measurements (e.g., for geochronology or for the study of fine isotope variation in nature) powerful instrumentation with high mass dispersion and multiple ion collector systems instead of single ion collection are commercially available on the analytical market. 

In another publication (13) it was demonstrated that with proper maintenance and operating care each of two HPLC solvent delivery systems was capable of delivering smooth, precise flow rates of as low as a few microliters per minute. While not all chromatographers will desire this high degree of precision, it is clear that if people observe good laboratory practice,... 

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