Pharmacokinetic disposition of erythraline in rats after intravenous administration

Demarque, Daniel P.; Callejon, Daniel R.; Pinto, Larissa G.; Gouvea, Dayana R.; de Moraes, Natália V.; Lopes, João L.C.; Lopes, José N.C.; Lopes, Norberto P.; Guaratini, Thais

doi:10.1016/j.bjp.2019.07.002

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Original articles • Rev. bras. farmacogn. 29 (6) • Nov-Dec 2019 • https://doi.org/10.1016/j.bjp.2019.07.002 linkcopy

Pharmacokinetic disposition of erythraline in rats after intravenous administration

Authorship SCIMAGO INSTITUTIONS RANKINGS

Erythraline is the major alkaloid produced by Erythrina verna Vell., Fabaceae, a plant used in folk medicine and phytotherapeutic products to treat anxiety and sleep disorders. This study aimed to investigate the pharmacokinetic parameters of erythraline after intravenous administration in rats. For the analysis of erythraline in rat plasma, a method was developed and validated using UHPLC-MS/MS. Pharmacokinetic parameters were estimated by non-compartmental analysis. The metabolite 8-oxo-erythraline observed in previous biomimetic model studies was monitored during in vivo experiments. The quantification limit was 5 ng/ml within a linear range of 5-2000 ng/ml. After an intravenous dose of 1 mg/kg, the following pharmacokinetic parameters were observed: elimination half-life of 44.2 min; total clearance of 42.1 ml/min/kg and volume of distribution of 2085 ml/kg. In summary, a precise, accurate and selective UHPLC-MS/MS method was developed and successfully applied to investigate the pharmacokinetics of erythraline in rats. The metabolite 8-oxo-erythraline was observed in rat plasma after 20 min of erythraline administration.

Keywords:
Pharmacokinetics; Natural products; Herbal medicine

Detection limit (ng/ml)	0.6
LLOQ (ng/ml)	5
Linearity	5-2000 ng/ml
	r² = 0.99
Intra-run precision (CV%, n = 5)
LLOQ (5 ng/ml)	6.18
LQC (15 ng/ml)	2.30
MQC (750 ng/ml)	2.81
HQC (1750 ng/ml)	3.40
Inter-run precision (CV%, n = 5)
LLOQ (5 ng/ml)	5.51
LQC (15 ng/ml)	6.52
MQC (750 ng/ml)	2.31
HQC (1750 ng/ml)	4.39
Intra-run accuracy (RSE, n = 5)
LLOQ (5 ng/ml)	1.05
LQC (15 ng/ml)	0.35
MQC (750 ng/ml)	1.29
HQC (1750 ng/ml)	4.25
Inter-run accuracy (RSE, n = 5)
LLOQ (5 ng/ml)	3.86
LQC (15 ng/ml)	5.96
MQC (750 ng/ml)	1.15
HQC (1750 ng/ml)	8.84

PK parameters	Median (25th-75th percentiles)
AUC_0-240 (µg/ml*min)	23.45 (16.75-32.76)
AUC_0-inf (µg.ml/min)	23.73 (17.12-33.42)
AUC_0-240/AUC^0-inf	0.98 (0.97-0.98)
t_1/2 (min)	44.23 (37.76-47.83)
MRT (min)	49.62 (46.30-52.11)
V_d (ml/kg)	2085.0 (1723.3-3782.1)
CL (ml/min/kg)	42.1 (33.7-74.6)

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[TFN1] LLOQ: lower limit of quantification; LQC: lower concentration quality control; MQC: medium concentration quality control; HQC: high concentration quality control; CV: coefficient of variation; RSE: relative standard error.