Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies

Table 1

The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog in rat plasma and brain homogenate (n = 3 batches, 6 replicates per batch).

Analytes	Matrix	Spiked conc. (ng/mL)	Intrabatch (n = 6)			Interbatch (n = 18)
			Measured conc. (ng/mL)	Precision (CV%)	Accuracy (%)	Measured conc. (ng/mL)	Precision (CV%)	Accuracy (%)
Brigatinib	Plasma	1.0	0.92 ± 0.11	11.95	92.00	0.95 ± 0.10	10.52	95.00
		2.0	2.03 ± 0.21	10.34	101.50	1.97 ± 0.18	9.14	98.50
		400	391.88 ± 28.99	7.39	97.97	408.28 ± 38.34	9.39	102.07
		1600	1514.40 ± 96.16	6.35	94.65	1548.96 ± 67.38	4.35	96.81
	Brain homogenate	0.5	0.45 ± 0.07	15.56	90.00	0.52 ± 0.06	11.53	104.00
		1.0	1.05 ± 0.11	10.47	105.00	0.96 ± 0.08	8.33	96.00
		200	190.78 ± 19.48	10.21	95.39	192.07 ± 14.10	7.34	95.39
		800	845.20 ±71.13	8.42	105.65	813.20 ± 51.13	6.29	101.65
Brigatinib-analog	Plasma	1.0	1.07 ± 0.13	12.15	107.00	1.06 ± 0.11	10.38	106.00
		2.0	1.87 ± 0.15	8.02	93.50	1.92 ± 0.14	7.29	96.00
		400	422.46 ± 39.09	9.25	105.62	402.53 ± 29.17	7.25	100.63
		1600	1537.96 ± 101.46	6.60	96.12	1557.67 ± 86.35	5.54	97.35
	Brain homogenate	0.5	0.53 ± 0.09	16.98	106.00	0.51 ± 0.07	13.73	102.00
		1.0	0.96 ± 0.10	10.42	96.00	0.97 ± 0.08	8.25	97.00
		200	208.54 ± 16.83	8.07	104.27	210.19 ± 15.26	7.26	105.10
		800	764.06 ± 54.21	7.09	95.51	781.64 ± 47.34	6.06	97.71