Determination of cepharanthine in rat plasma by LC–MS/MS and its application to a pharmacokinetic study

Figures & data

Figure 1. Chromatograms of blank plasma (A); plasma spiked with CPA and rutin (B); rat plasma sample obtained 10 h after oral administration of CPA (C). 1: rutin; 2: CPA.

Table 1. The intra-day and inter-day precision and accuracy of cepharanthine in plasma samples.

		Intra-day			Inter-day
Analyte	Plasma samples (ng/mL)	Concentration measured (ng/mL)	Precision (%, RSD)	Accuracy (%, RE)	Concentration measured (ng/mL)	Precision (%, RSD)	Accuracy (%, RE)
Cepharanthine	0.2	0.19	6.87	–5	0.22	5.64	10
	10	10.57	5.59	5.70	9.14	7.52	–8.60
	150	141.25	6.38	–5.83	161.25	8.24	7.50

Table 2. Stability of CPA in plasma samples (n = 3).

		Stability (%, RE)
Analyte	Plasmasamples (ng/mL)	Short-term (24 h at room temperature)	Long-term (30 days at –40 °C)	Three freeze (–40 °C)–thaw (room temperature) cycles
CPA	0.2	4.68	–7.39	7.68
	10	7.45	7.25	6.87
	150	5.36	6.98	9.77

Figure 2. The pharmacokinetic profiles of CPA in rats after intravenous administration of CPA (A) at dosage of 1 mg/kg and oral administration of CPA (B) at 10 mg/kg.

Table 3. Pharmacokinetic parameters of CPA in rats after intravenous (1 mg/kg) or oral administration (10 mg/kg) of CPA (n = 6, mean ± SD).

Parameters	Intravenous	Parameters	Oral
Tmax (h)	–	Tmax (h)	2.67 ± 1.16
Cmax (ng/mL)	153.7 ± 16.18	Cmax (ng/mL)	46.89 ± 5.25
t1/2 (h)	6.76 ± 1.21	t1/2 (h)	11.02 ± 1.32
AUC(0–t) (ng·h/mL)	717.81 ± 158.35	AUC(0–t) (ng·h/mL)	406.63 ± 62.57
AUC(0–inf) (ng·h/mL)	721.80 ± 160.76	AUC(0–inf) (ng·h/mL)	422.26 ± 66.91
MRT(0–t) (h)	7.04 ± 0.49	MRT(0–t) (h)	10.49 ± 0.62
MRT(0–inf) (h)	7.30 ± 0.51	MRT(0–inf) (h)	12.45 ± 1.20
Clz (L/h/kg)	1.431 ± 0.31	Clz/F (L/h/kg)	24.08 ± 2.42
Vz (L/kg)	13.79 ± 1.76	Vz/F (L/kg)	381.37 ± 61.63

C_max: peak plasma concentration; T_max: the corresponding time to reach C_max; t_1/2: the terminal elimination half-life; MRT: mean residence time; AUC_0–t: AUC_(0–inf): the areas under the plasma concentration–time curve from time zero to the last quantifiable time-point and to infinity; CLz: clearance; Vz: apparent volume of distribution.