Development and validation of equilibrium dialysis UHPLC-MS/MS measurement procedures for total and unbound concentrations of bictegravir, dolutegravir, darunavir and doravirine in human plasma. Application to patients with HIV.

Background: Fixed-dose combinations of antiretroviral drugs are commonly used to treat HIV infection and therapeutic monitoring is not part of routine clinical practice. However, drug concentrations monitoring might have role in different clinical scenarios as well as for research purposes. This study aimed to develop and validate UHPLC-MS/MS procedures for measuring total and unbound concentrations of bictegravir, dolutegravir, darunavir and doravirine in human plasma.

Results: No significant interferences or carry-over were observed. Imprecisions, absolute relative biases, normalised matrix effects and recoveries were ≤15.0 %, ≤11.1 %, (94.7-104.1)% and (96.7-105.5)%, respectively. Non-linear measuring intervals were observed between (25-10,000) µg/L for total/plasma dialysate concentrations and linearity schemes (1.00-100) µg/L for buffer dialysate concentrations.

Conclusion: No significant interferences or carry-over were observed. Imprecisions, absolute relative biases, normalised matrix effects and recoveries were ≤15.0 %, ≤11.1 %, (94.7-104.1)% and (96.7-105.5)%, respectively. Non-linear measuring intervals were observed between (25-10,000) µg/L for total/plasma dialysate concentrations and linearity schemes (1.00-100) µg/L for buffer dialysate concentrations.