To determine the shortest distance between two particles A and B, first establish the distance as a function of time based on their velocities and initial positions. The cosine rule can be applied if the angle between the particles is known, specifically if it is 90 degrees. Next, calculate the first derivative of the distance function to identify the time at which this distance is minimized. Finally, substitute this time back into the distance function to find the minimum distance. This approach effectively utilizes calculus and trigonometry to solve the problem.