Table 4.

The observed and relative retentions of ketamine (Ket) and its metabolites achieved using the achiral chromatographic separation developed in this study.

Compound	Peak	Retention (min)	Retention Factor	MRM Ion Transition
(R.S)-Ketamine*	1	20.7	3.50	238 → 115
(R,S)-Norketamine*	2	18.7	3.06	224 → 125
(R,S)-Dehydronorketamine*	3	18.2	2.96	222 → 177
(2S,6S); (2R,6R)-Hydroxynorketamine*	4a	13.7	1.98	240 → 125
(2S,6R); (2R,6S)-Hydroxynorketamine*	4b	20.9	3.54	240 → 125
(2S,5S); (2R,5R)-Hydroxynorketamine	4c	14.6	2.17	240 → 125
(2S,4S); (2R,4R)-Hydroxynorketamine	4d	15.5	2.37	240 → 125
(2S,4R); (2R,4S)-Hydroxynorketamine	4e	15.8	2.43	240 → 125
(2S,5R); (2R,5S)-Hydroxynorketamine	4f	18.7	3.07	240 → 125
(2S,6S); (2R,6R)-Hydroxyketamine*	5a	14.5	2.15	254 → 151
(2S,6R); (2R,6S)-Hydroxyketamine*	5b	18.9	3.11	254 → 151
(2S,5S); (2R,5R)-Hydroxyketamine	5c	15.5	2.37	254 → 151
(2R,5S)-Hydroxyketamine	5d	16.9	2.67	254 → 151
(2S,6S); (2R,6R)-Hydroxynorketamine glucuronide	6a	4.9	0.07	416 → 125
Hydroxynorketamine glucuronide	6b	7.4	0.61	416 → 125
Hydroxynorketamine glucuronide	6c	8.3	0.80	416 → 125
Hydroxynorketamine glucuronide	6d	9.9	1.15	416 → 125
Hydroxynorketamine glucuronide	6e	13.5	1.93	416 → 125
(R,S)-D₄-Ketamine*	7	20.5	3.46	242 → 129

The retention time of a compound was identified using standards and microsomal incubates obtained with (R)-Ket and (S)-Ket and the established structures are denoted by *. No attempt was made to establish the stereochemistries of the glucuronide metabolites. The retention factors were determined. The multiple reaction monitoring (MRM) ion transitions presented in the table were used to quantify the compounds in the validation studies and in the application to the analyses of plasma and urine samples from a CRPS patient undergoing treatment with (R,S)-Ket.