HISTORY OF FLIGHTOn October 16, 2019, about 2333 central daylight time, a Piper PA-23-250, N778PA, was presumed destroyed when it was involved in an accident in the Gulf of Mexico. The pilot is presumed to have been fatally injured. The airplane was operated under the provisions of Title 14 Code of Federal Regulations Part 91 as a personal flight. The airplane departed from the Cape Girardeau Regional Airport (CGI), Cape Girardeau, Missouri, about 1836 and was reportedly en route to the Louisiana Regional Airport (REG), Gonzales, Louisiana. The airplane was not in communication with any air traffic control facility. The airplane was equipped with automatic dependent surveillance – broadcast (ADS-B) equipment and the airplane's flight track was obtained from the Federal Aviation Administration. The data showed the airplane take off from CGI, after which it assumed a heading of about 190°. The first portion of the flight was conducted at an altitude of about 15,000 ft msl and the airplane remained on a heading of about 190°. About 2038, when the airplane was about 120 nm from REG it made a slight course correction to the right of about 5° and descended to about 6,500 ft msl. About 2118, the airplane passed over REG but made no course correction or altitude change. The airplane continued on the same heading and altitude until the final recorded data point at 2332 showed the airplane over the Gulf of Mexico, about 360 nm and 187° from REG. According to the data, the airplane had been airborne about 5 hours. A search for the airplane was conducted, but the airplane was not located. PERSONNEL INFORMATIONThe pilot logbooks were not available for review. AIRCRAFT INFORMATIONThe airplane maintenance records were not available for review. AIRPORT INFORMATIONThe airplane maintenance records were not available for review.