Development and validation of an LC-MS/MS method for monitoring larotrectinib, a tropomyosin-related kinase inhibitor, in mouse and human plasma and application to pharmacokinetic studies

Journal of Analytical Science and Technology

Table 1 Reproducibility and accuracy for larotrectinib in mice and human plasma (n = 5)

	Theoretical concentration (ng/mL)
	LLOQ	LQC	MQC	HQC
	5	15	500	8000
*Mice*
(A) Intra-day accuracy and precision
Mean estimated concentration (ng/mL)	4.90	14.42	495.89	8127.24
Precision (RSD^a, %)	2.62	2.76	2.99	1.37
Accuracy (RE^b, %)	− 1.99	− 3.87	− 0.82	1.59
(B) Inter-day accuracy and precision
Mean estimated concentration (ng/mL)	4.64	14.90	524.64	8284.02
Precision (RSD^a, %)	6.93	1.26	6.46	0.63
Accuracy (RE^b, %)	− 7.27	− 0.64	4.93	3.55
*Human*
(A) Intra-day accuracy and precision
Mean estimated concentration (ng/mL)	4.55	15.27	511.22	8100.98
Precision (RSD^a, %)	10.48	0.77	0.44	1.21
Accuracy (RE^b, %)	− 8.99	1.78	2.24	1.26
(B) Inter-day accuracy and precision
Mean estimated concentration (ng/mL)	5.34	15.18	525.40	8223.77
Precision (RSD^a, %)	4.06	2.63	1.90	2.42
Accuracy (RE^b, %)	6.77	1.17	5.08	2.80

^astandard deviation of concentration/mean concentration × 100%
^b(calculated concentration − theoretical concentration)/theoretical concentration × 100%