Recent Advances in the Study of the Inclusion Complex Darunavir-β-Cyclodextrin by LC-MS.
Darunavir is a protease inhibitor used in the treatment of human immunodeficiency virus (HIV) infection. This work proposes a LC-MS method indicative of stability for the determination of darunavir in the complex darunavir-β-cyclodextrin, a recent advance for the use of antiretroviral. The method was completely validated according to the International Conference on Harmonization guidelines, showing accuracy, precision, selectivity, robustness, and linearity. The separation was achieved on a 250 mm × 4.6 mm CN Luna column with water +0.1% glacial acetic acid-acetonitrile +0.1% glacial acetic acid, 60 + 40 (v/v) at phase at a flow rate of 1.0 mL/min. UV detection was performed at 268 nm at 25°C. Mass spectral analyses were performed with electrospray ionization ion source and ion trap mass analyzer. The method was linear over the concentration range of 10-60 μg/mL with correlation coefficients at 1.000 and LODs and LOQ of 1.13 and 3.43 μg/mL, respectively. The drug for HIV infection was subjected to acid, basic, oxidative, and neutral degradation and photolysis. Degradation products were identified by LC-MS and LC-tandem MS; therefore, the method can be regarded as indicative of stability. The validated method is very useful to the routine quality control for quantification of darunavir in inclusion complex darunavir-β-cyclodextrin.