Well, this is a tough question and can only be answered by the concerned employee. However, when you notice the following situations, if MIGHT be the right time to quit.
# When you no longer find fulfilment doing your job. There are a few instances when you suddenly begin to hate everything about your job. At this point, you lost your fulfilment and get frustrated most times. It could be that the right time to leave has come.
# When your employer doesn't value you. Humans do not only work to make a living. We sometimes also work to earn the respect of others. When you notice that your employer has stopped giving you the respect that you deserve, it could mean that the right time to leave has come.
# When you've got an alternative income. Once you're able to make far more than your salary from alternative income sources, it could mean that you have to quit, so that you can get enough time to oversee your own business.
I hope that this helps.