Vented filter for automatic HPLC loop loading

A vented filter is placed at the HPLC (High Performance Liquid Chromatography) loop entry port of an HPLC injector valve. The vented filter prevents the push gas used to deliver the crude radiolabeled product from over-pushing the liquid to waste. Push gas is vented off when the entire crude liquid product has passed through the vented filter and been loaded onto the HPLC loop.

TECHNICAL FIELD

The present invention is in the field of automated radiochemistry. More specifically, the invention relates to automated HPLC (High Performance Liquid Chromatography) purification of radiotracers or radiolabeled pharmaceuticals.

BACKGROUND OF THE INVENTION

Chromatography is used to separate mixtures of substances into their individual components. The basic principles of chromatography involve a stationary phase (usually a solid or a liquid supported on a solid) and a mobile phase (usually a liquid or a gas). The mobile phase flows through the stationary phase and carries the components of the mixture with it. Since different components travel at different rates, the components separate from each other during the process and can be isolated.

In column chromatography, stationary phase particles are packed into a column and the mobile phase is allowed to flow through the stationary phase. This method relies on gravity to force the mobile phase through the stationary phase. During column chromatography, the smaller the stationary phase particle size, the greater the separation of components. However, smaller particles have greater resistance to flow.

HPLC is an improved form of column chromatography. Instead of a solvent being allowed to drip through a column under gravity, it is forced through the column under high pressures of up to 400 atmospheres, thereby increasing the speed of the process and allowing the use of smaller stationary phase particles. Thus, HPLC allows for improved separation of the components of the mixture.

FIG. 1is a schematic of a conventional HPLC system100. A sample mixture120is introduced to system100through injector valve130. Injector valve130allows sample120to be introduced into HPLC loop140with any excess sample120directed to waste110. Once sample120is in HPLC loop140, injector valve130is activated to allow mobile phase160to be pumped into system100via pump150. Pump150forces mobile phase160through injector valve130and HPLC loop140and into column170. Column170is filled with a stationary phase175. As mobile phase160is forced through injector valve130, HPLC loop140, and column170, the individual components of sample120are separated out. As the separated components flow out of the column, detector180analyzes the results.

One common method of detecting substances that have passed through the column uses ultra-violet absorption. Many organic compounds absorb UV light of various wavelengths. Therefore a beam of UV light is directed through the stream of liquid coming out of the column and detected on the opposite side of the stream. The amount of light absorbed will depend on the amount of a particular compound that is passing through the beam at the time. Based on the output of the detector, it is possible to identify the separated components of the sample.

Conventional HPLC is often employed as a method of analysis of different components in a given sample. In the production of radiolabeled pharmaceuticals, the radiolabeled pharmaceutical synthesis step is often followed by a purification step. HPLC is one purification method to isolate the radiolabeled pharmaceutical from the synthesis mixture. In a radiolabeled pharmaceutical HPLC purification system, a radiation detector is used along with the UV detector to identify the components of the sample. The detection of a peak in the UV or radiation detector signal indicates the presence of the radiolabeled pharmaceutical. A valve following the detectors is installed to direct fluid flow to either a waste vial or to a product collection vial. Once the UV chromatogram peak or the radiation chromatogram peak of the desired radiolabeled pharmaceutical appears, the valve is switched to collect this product.

As mentioned above, the first step of the HPLC process is to load a specific amount of the sample to be purified/separated into a fixed volume HPLC loop. The other end of the loop is directed to waste to catch any waste that overflows from the loop. In a regular HPLC setup, the sample is injected into the loop with a syringe and overflows to waste are common. However, in the production of radiolabeled pharmaceuticals, it is desirable to avoid overflows to waste, thereby minimizing process loss. Further complicating the process is that the task of loading the loop is often automated.

One efficient way of transporting liquid is by using a push gas to push liquid through a series of tubes. The push gas has to be turned off at the right time to avoid sending the crude radiolabeled product to waste. Prior systems use a bubble detector or a liquid detector to determine when the radiolabeled product has been completely loaded into the HPLC loop and to stop the push gas. However, these systems are unreliable.

Therefore, it is desirable to have a reliable device to automatically limit the amount of sample that is injected into the HPLC loop.

SUMMARY OF THE INVENTION

With a vented filter at the HPLC loop entry port of an HPLC injector valve, the push gas used to deliver the crude radiolabeled product will not over push the liquid to waste. Push gas is vented off when the entire crude liquid product has passed through the vented filter and been loaded onto the HPLC loop.

DETAILED DESCRIPTION OF THE INVENTION

As required, disclosures herein provide detailed embodiments of the present invention; however, the disclosed embodiments are merely exemplary of the invention that may be embodied in various and alternative forms. Therefore, there is no intent that specific structural and functional details should be limiting, but rather the intention is that they provide a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention.

As mentioned above,FIG. 1discloses a conventional High Performance Liquid Chromatography (HPLC) system100. A mixture sample120is introduced to system100through injector valve130. Sample120may be a radiolabeled product such as a radiolabeled pharmaceutical. Injector valve130allows sample120into HPLC loop140with any excess sample120directed to waste110.

Once sample120is in HPLC loop140, injector valve130is switched to allow mobile phase160to be pumped through the HPLC loop via pump150. Mobile phase160may be any suitable eluent. Furthermore, mobile phase160may consist of a plurality of eluents used successively to help promote greater separation of the components of the sample.

Pump150forces mobile phase160through injector valve130and HPLC loop140and into column170. Pump150may be able to force mobile phase160through at pressures upwards of 400 atmospheres. Column170is filled with a stationary phase175. Stationary phase175may consist of particles with a diameter of less than ten microns. As mobile phase160is forced through injector valve130, HPLC loop140, and column170, the components of sample120are chromatographically separated out. Once the separation is complete, detector180analyzes the results. Detector180may be an ultraviolet absorption detector and/or a radiation detector. Once the UV chromatogram peak or the radiation chromatogram peak of the desired radiolabeled pharmaceutical appears, a valve located downstream from the detectors is switched to collect the product. After the chromatogram peak of the desired product has passed, the valve is switched back to waste.

FIGS. 2(a) and2(b) are close-up views of the area within the dashed box inFIG. 1, modified in accordance with the present invention.FIG. 2(a) depicts the present invention in the state of injecting the sample230through injector valve130into HPLC loop140. Sample230is pushed through sample feed tube250by a gas240. The sample passes through vented filter210as it enters injector valve130.

FIG. 2(b) depicts the system of the present invention once the gas240has reached vented filter210. i.e., after all of the liquid sample230has passed through the vented filter210and loaded onto the HPLC loop. To prevent the gas240from pushing sample230into waste tube220, the gas240is vented off by vented filter210, thereby precluding gas240from entering into the HPLC loop.

Vented filter210may be located such that a set amount of sample230is allowed to enter HPLC loop140before the gas240is vented off. Vented filter210may be any device capable of venting of gas from a feed tube.

While the invention has been disclosed with reference to specific exemplary embodiments, modifications to and departures from the disclosed embodiments will occur to those having skill in the art. Accordingly, what is protected is defined by the scope of the following claims.