New IMS sample injector facilitates cleaning validation.(In the field: pharmaceutical science & technology news)(ion mobility spectrometry )

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Pharmaceutical Technology , 06/01/2004 28 6

New IMS sample injector facilitates cleaning validation.(In the field: pharmaceutical science & technology news)(ion mobility spectrometry ) Bush, Laura *~|~*

COPYRIGHT 2004 Advanstar Communications, Inc.

To provide analysts a better method of introducing cleaning validation samples into their ion mobility spectrometry (IMS) systems, Smiths Detection (Warren, NJ) has added a high-performance injector (HPI) to its "Ionscan" line of IMS technologies. According to the company, the injector increases control over the sample-introduction conditions and improves the reproducibility of the results, making them comparable to the results achieved with the use of traditional high-performance liquid chromatography (HPLC) systems. IMS detects and identifies compounds by measuring the mobility of ions in the gas phase. In a cleaning validation process, samples are taken using standard swabbing techniques, extracted into a solvent, and injected into the Ionscan using an autosampler.
With the system's original injection method, the sample is injected into a PTFE substrate. With the new HPI, the sample is injected into a glass capillary that can be configured for the needs of the application, under precisely controlled airflow and temperature conditions. "The HPI allows us to get reproducibility very similar to what is achieved with HPLC and offers the user a lot of flexibility," notes Robert Sandor, PhD, vice-president for life sciences at Smiths.
Analysis of the sample begins with thermal desorption to vaporize the zample. Once the sample is in the vapor phase, an airstream carries it into the ionization section of the instrument, where it is selectively ionized.
Selective ionization is conducted using atmospheric chemical ionization, in either negative or positive mode, using an appropriate dopant to provide the desired selectivity. "We don't generally fragment these compounds," notes Reno DeBono, PhD, director of research and development for life sciences at Smiths. "We work with molecular ions."
With IMS, compounds are identified on the basis of the speed at which the ions travel through a drift tube, which depends on their size and shape. Ions are gated into a drift tube with the use of an electric field with a gradient of 2000 V and with air flowing in the opposite direction at atmospheric pressure. When the ions reach the end of the tube, they strike a plate, producing an electric current, which is then measured. The strength and speed of the ions' passage through the drift tube is displayed in a plasmogram, very similar to a chromatogram. Typical drift times are between 10 and 20 ms. Accurate identification is based on the detection of peaks within [+ or -] 0.04 ms of their expected peak positions.
The IMS method is useful for distinguishing compounds having similar properties and characteristics. Sandor cites the example of comparing hexane and benzene. Although they have a very similar molecular weight, benzene is stiff and pancake-shaped, and hexane is like a flexible wire. "Because of their different shapes, even if their molecular weights were identical, the IMS can distinguish them," notes Sandor. "We even have customers who have preliminary evidence that they can distinguish between diastereomers [molecules with two or more chiral centers]," adds DeBono.
Sandor says the sensitivity of IMS is similar or better than that of HPLC. "For HPLC, the best sensitivity I've aware of is about 0.2 ng," he says. Although the sensitivity of the Ionscan varies depending on the compounds involved, the system can detect quantities from 0.01 to 10 ng of many pharmaceutical compounds. In tests conduced with diazepam, the instrument was able to detect quantities as low as .004 ng.
The system does have limitations in terms of the types substances it can detect. "The compound has to be vaporizable and ionizable, and have a maximum molecular weight of about 1200," says Sandor, which means that the system cannot be used with large biopharmaceutical ingredients such as peptides. "As a general rule, the IMS can detect approximately 80% of the APIs we test it with," he concludes.
Sandor says that 5 out of the top 10 largest pharmaceutical companies are using the system for cleaning validation in pilot-production facilities, and one in commercial production. "There are about 25 validated methods that have been reported back to us from our customers," he says. Controlled studies are currently being conducted, the results of which are expected to be published later this year.
The main advantages for IMS cited by the company are its speed and simplicity of use. Typical throughput time for the IMS is 60-102 s, which is faster many standard HPLC methods that can take 10-20 min. This speed can reduce the length of equipment downtime that occurs between batches while cleaning validation is conducted.

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