TY - JOUR
T1 - Pharmacokinetics and tissue distribution of novel platinum containing anticancer agent BP-C1 studied in rabbits using sector field inductively coupled plasma mass spectrometry
AU - Navolotskii, Denis V.
AU - Ivanenko, Natalya B.
AU - Solovyev, Nikolay D.
AU - Fedoros, Elena I.
AU - Panchenko, Andrey V.
N1 - Publisher Copyright:
© 2015 John Wiley & Sons, Ltd.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - A method of platinum quantification in whole blood samples after microwave digestion using sector field inductively coupled plasma mass spectrometry has been developed. The following analytical figures of merit have been established: limit of detection 1.1 μg/L for blood samples, dynamic range 3.6-200 μg/L, intra-day precision (relative standard deviation, n = 9) did not exceed 5%. Spiked samples were analyzed for method validation. The method was used for pharmacokinetics studies of a novel anti-cancer drug BP-S{cyrillic}1, a complex of cis-configured platinum and benzene-poly-carboxylic acids. Main pharmacokinetic parameters (area under curve, maximum concentration, clearance, half-life times for α- and β-phase) were estimated for two dosage forms of BP-C1 0.05 and 0.125 mass %. Pharmacokinetic curves were assessed for single and course administration. Studies were performed using rabbits (n = 6) as a model. BP-C1 was injected intramuscularly. The study established dose proportionality of the tested dosage forms and suggested clinical dosing schedule: 5 days of injections followed by 2 days' break. Platinum tissue distribution was studied in tissue samples collected 20 days after the last injection. Predominant platinum accumulation was observed in kidneys, liver, and muscles near injection site. 'Slow' phase of platinum excretion kinetics may be related to the muscles at the injection site.
AB - A method of platinum quantification in whole blood samples after microwave digestion using sector field inductively coupled plasma mass spectrometry has been developed. The following analytical figures of merit have been established: limit of detection 1.1 μg/L for blood samples, dynamic range 3.6-200 μg/L, intra-day precision (relative standard deviation, n = 9) did not exceed 5%. Spiked samples were analyzed for method validation. The method was used for pharmacokinetics studies of a novel anti-cancer drug BP-S{cyrillic}1, a complex of cis-configured platinum and benzene-poly-carboxylic acids. Main pharmacokinetic parameters (area under curve, maximum concentration, clearance, half-life times for α- and β-phase) were estimated for two dosage forms of BP-C1 0.05 and 0.125 mass %. Pharmacokinetic curves were assessed for single and course administration. Studies were performed using rabbits (n = 6) as a model. BP-C1 was injected intramuscularly. The study established dose proportionality of the tested dosage forms and suggested clinical dosing schedule: 5 days of injections followed by 2 days' break. Platinum tissue distribution was studied in tissue samples collected 20 days after the last injection. Predominant platinum accumulation was observed in kidneys, liver, and muscles near injection site. 'Slow' phase of platinum excretion kinetics may be related to the muscles at the injection site.
KW - Benzene-poly-carboxylic acids
KW - Breast cancer
KW - Inductively coupled plasma mass spectrometry
KW - Pharmacokinetics
KW - Platinum
UR - http://www.scopus.com/inward/record.url?scp=84940955394&partnerID=8YFLogxK
U2 - 10.1002/dta.1824
DO - 10.1002/dta.1824
M3 - Article
C2 - 26061351
AN - SCOPUS:84940955394
SN - 1942-7603
VL - 7
SP - 737
EP - 744
JO - Drug Testing and Analysis
JF - Drug Testing and Analysis
IS - 9
ER -