IS provides facilities for detecting duplicates. You might need to modify your integration a bit to let it do so. Refer to the docs for details.
Probably the easiest approach is to simply record the PO numbers that you process into a DB table. At the start, read for the PO number. If present, stop. If not, proceed and then record the PO number in the table.
Depending upon volume and how long this solution stays in place, you may need a scheme for purging old/expired PO numbers from the table to reclaim space.
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