Abstract A stability study for amodiaquine (AQ) and desethylamodiaquine (AQm) in whole blood and plasma is reported. AQ, AQm and chloroquine (CQ) were simultaneously analysed and the ratios AQ/CQ and AQm/CQ were used to ensure correct interpretation of the stability results. CQ was stable in whole blood and plasma at all tested temperatures enabling it to be a stability marker in stability studies. Simultaneous analysis of compounds, of which at least one is already known to be stable, permits a within sample ratio to be used as a stability indicator. The new approach significantly reduced bias when compared to the traditional approach. AQ and AQm were stable in plasma at −86 °C and −20 °C for 35 days, at 4 °C for 14 days and at 22 °C for 1 day. AQ and AQm were stable in blood at −86 °C and 4 °C for 35 days, at −20 °C and 22 °C for 7 days and at 37 °C for 1 day.