In this work, stability and the pH-sensitivity of pH-sensitive stealth liposomes containing cisplatin
exposed to plasma medium and their subsequent responses to pH modifications were evaluated. A
method to determine platin in mouse plasma by electrothermal atomic absorption spectroscopy (ET
AAS) was developed and validated. At first, a comparative study of sample preparation treatments with
basic, acidic, and acidic added with Triton X-100 as a modifier was done. The best treatment was obtained
with HCl 3% (v/v). The ET AAS method with acid treatment presented linearity at a range of 10–160 ng
Pt/mL. The limits of detection (LOD) was 3.1 ng/mL Pt for acid treatment, while the limit quantification
(LOQ) was 10 ng/mL Pt. The acid treatment presented good repeatability (VC < 15.0%) and recovery close
to 100%. This treatment was chosen for subsequent studies due to its best value of repeatability, recovery,
LOD and lowest cost. pH-sensitive stealth liposomes, containing cisplatin, demonstrated low stability and
poor response to pH variation after plasma incubation. These findings suggest that further studies are
needed to improve liposome formulation i.e., to reduce its size.