Simultaneous Determination of Parecoxib and Its Metabolite Valdecoxib Concentrations in Beagle Plasma by UPLC-MS/MS and Application for Pharmacokinetics Study

Figures & data

Figure 1 The chemical structure of parecoxib, valdecoxib and celecoxib (IS) (A) parecoxib, (B) valdecoxib, (C) celecoxib (IS).

Table 1 MS Parameters of Two Analytes and IS

Analytes	ESI Source	RT (min)	Parent (m/z)	Daughter (m/z)	Cone (V)	Collision (V)
Parecoxib	–	1.41	368.97	119.01	10	38
Valdecoxib	–	1.36	312.89	118.02	30	25
Celecoxib	–	1.48	379.98	316.02	20	20

Figure 2 The ion transitions from parent ion to daughter ion of (A) Parecoxib, (B) valdecoxib, (C) Celecoxib.

Figure 3 (A) a blank plasma sample, (B) a blank plasma sample spiked with parecoxib, valdecoxib and IS, (C) a beagle plasma sample 1.5 h after injection of parecoxib.

Table 2 Regression Equation, Linear Ranges, Correlation Coefficients and LLOQ of Two Analytes

Analytes	Regression Equation	Linear Ranges (ng/mL)	R^2	LLOQ (ng/mL)
Parecoxib	y = 0.0151 x - 0.1342	5–4000	0.9999	5
Valdecoxib	y = 0.1744 x - 0.0206	5–4000	0.9998	5

Table 3 Precision and Accuracy of Parecoxib and Valdecoxib in Beagle Plasma (n=6, Mean ± SD)

Compounds	Spiked (ng/mL)	Intra-Day		Inter-Day
		RSD (%)	RE (%)	RSD (%)	RE (%)
Parecoxib	10	3.65	−1.38	5.91	−0.33
	800	2.81	−0.57	3.85	0.45
	3000	1.67	−0.76	2.28	−0.54
Valdecoxib	10	3.22	−0.51	4.71	−0.49
	800	2.39	1.96	3.91	−0.43
	3000	1.36	−0.68	2.41	−0.25

Table 4 The Recoveries and ME of Parecoxib, Valdecoxib and IS in Beagle Plasma (n=6, Mean ± SD)

Compounds	Spiked (ng/mL)	Recoveries (%)	ME (%)
Parecoxib	10	83.46 ± 2.70	99.64 ± 2.95
	800	83.06 ± 3.98	100.17 ± 4.76
	3000	87.58 ± 0.62	99.75 ± 4.15
Valdecoxib	10	88.87 ± 2.23	102.29 ± 2.33
	800	89.69 ± 0.94	99.98 ± 1.99
	3000	82.54 ± 2.37	100.50 ± 4.29
IS	50	81.53 ± 3.34	97.13 ± 5.54

Table 5 The Stability of Parecoxib and Valdecoxib in Beagle Plasma (n=6, Mean ± SD)

Compounds	Spiked (ng/mL)	Room Temperature, 12 h		Autosampler 4 °C, 12 h		Three Freeze-Thaw		−20°C, 4 weeks
		RSD(%)	RE(%)	RSD(%)	RE(%)	RSD(%)	RE(%)	RSD(%)	RE(%)
Parecoxib	10	2.76	−0.41	3.09	0.37	2.91	−0.75	1.78	−1.96
	800	2.49	2.94	2.52	3.95	1.98	2.38	1.46	0.33
	3000	2.11	0.23	2.21	−1.20	1.57	−0.42	1.79	0.60
Valdecoxib	10	2.47	−0.59	3.12	−1.04	2.09	0.27	4.64	−1.88
	800	3.84	−0.74	4.44	−2.71	4.58	1.70	3.06	−1.93
	3000	1.09	−1.09	2.50	−0.73	1.21	1.90	2.28	−0.29

Table 6 The Stock Solution Stability of Parecoxib, Valdecoxib and IS in Beagle Plasma (n=6)

Compounds	Spiked (μg/mL)	Room Temperature, 12 h		−20°C, 3 weeks
		RSD (%)	RE (%)	RSD (%)	RE (%)
Parecoxib	10	3.72	−1.83	2.59	2.67
Valdecoxib	10	3.10	1.33	3.51	−2.17
IS	10	3.56	−3.33	4.29	−2.83

Table 7 Pharmacokinetic Parameters of Parecoxib and Valdecoxib After Intramuscular Injection of 1.33 mg/kg Parecoxib (n=6, Mean ± SD)

Parameters	Parecoxib	Valdecoxib
t1/2 (h)	3.39±2.32	2.27±1.22
Tmax (h)	0.20±0.07	1.36±0.34
MRT(0-t) (h)	1.50±0.18	2.46±0.45
MRT(0-∞) (h)	1.66±0.25	2.52±0.47
Cmax (ng/mL)	1967.59±418.18	1944.84±247.68
AUC(0-t) (ng·h/mL)	2502.79±370.09	4960.31±630.49
AUC(0-∞) (ng·h/mL)	2508.19±368.28	4967.02±629.81

Abbreviations: t_1/2, Half-life; T_max, Time of peak concentration; MRT_(0-t), Mean residence time of 0-t time; MRT_(0–∞), Mean residence time of 0-infinity time; C_max, Peak concentration; AUC_(0-t), Area under curve of 0-t time; AUC_(0-∞), Area under curve of 0-infinity time.

Figure 4 The mean plasma concentration-time curve of parecoxib and valdecoxib (zoomed 1 h to 4 h pharmacokinetic profile).