ICIVET-LITORAL   24728
INSTITUTO DE CIENCIAS VETERINARIAS DEL LITORAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SALIVA: A NEW CHALLENGE FOR ANTIRETROVIRALS DETECTION? Insights from mass spectrometry
Autor/es:
BALDO, MATÍAS N; HUNZICKER, GABRIEL A; MURGUIA, MARCELO C; HEIN, GUSTAVO J
Lugar:
Córdoba
Reunión:
Congreso; 3era Reunión Internacional de Ciencias Farmacéuticas RICIFA 2014; 2014
Institución organizadora:
Colegio Farmaceutico de Córdoba
Resumen:
Saliva contains
only the non-protein-bound fraction of total drug and allows an adequate
correlation between drug concentration and its pharmacological effect. The
antiretroviral Efavirenz (EFV) needs constant monitoring and comparative relative bioavailability
(RBA) studies of EFV in an alternative matrix required advanced technology.
The main objectives were: (i) to develop and to validate a simple method
by UFLC-MS/MS useful for a RBA study with human saliva and (ii) to find a
correlation between saliva and plasma results.
A C18 column (100 mm x 2.1 mm, i.d, 3 µm)
was used. Elution was performed in an isocratic mode using: methanol?water
(10:90 (v/v)), and 5mM ammonium formate in 97% MeOH as mobile phase. Sample
preparation involved a simple protein precipitation and dilution.
An RBA study of 600 mg EFV tablets was performed in
a single-dose, randomized-sequence, open-label, two-way crossover study, in 16 healthy
men. Saliva and plasma samples were taken at the same time. Pharmacokinetic
parameters were calculated by WinNonlin®.
The method showed linearity (r >0.999) over the
working range (1.00?99.85 ng/mL). Accuracy (85-115%) and precision (%CV<15)
were according to the international bioequivalence criteria. Cmax,
AUC0-t and AUC0-∞ for test and reference formulations were:
(24.19 and 29.41) ng/mL, (539.82 and 795.24) ng/mL/h, (702.45 and 951.85) ng/mL/h,
respectively. These results were comparable to those thrown by the study in plasma, which was performed by HPLC-UV-vis (λ=250 nm). The EFV concentration
could be obtained in saliva by the relation: [Saliva EFV] = 0.009 [Plasma EFV].
There was a good linear correlation (r =0.84) between the EFV concentrations in
both fluids.
A rapid and accurate UFLC-MS/MS method was developed. Saliva demonstrated to
be a suitable surrogate to evaluate EFV tablet pharmacokinetics and it has been
fairly comparable to plasma with excellent biosafety advantages for RBA and therapeutic drug monitoring studies.