Lithium Orotate Dissociation

It is something of an open question as to whether lithium orotate (LiOr) dissociates in solution (free Li+ and the base orotate), or whether it remains as an metalorganic complex.

This should be approachable by measuring 3 characteristics of LiOr solutions:

1. conductivity -- higher conductance implies free ions

2. osmolality -- higher osmolality implies dissociation

3. free Li+ concentration -- Li-selective electrode will detect Li+ if dissociated, but not in LiOr complex.

Conductivity

From Aron 2025 et al:

 Conductivity measurements
 To measure the conductivity of Li salts, the salts were dissolved in water
 to achieve Li concentrations of 4.3 mEq l−1, 430 μEq l−1, 43 μEq l−1 or
 21.5 μEq l−1 in each case. Conductivity was measured using an ST300C
 conductivity meter (OHAUS, 83033964) equipped with a STCON7
 electrode (OHAUS, 30080693) calibrated with potassium chloride
 conductivity standards. For each lithium salt, three independent solu-
 tion replicates (n = 3) were prepared. Conductivity values are reported
 in μS per cm at 25 °C.

Free Li+ Concentration

NT Sensors Li ISE

Osmolality

Wescor Vapro 5520 osmometer

Test Solutions

Make mixtures of LiCl, Li₂CO₃, and LiOr and several "physiological" solutions. Measure free Li+ with electrode. For Tris and plasma, also measure osmolality.

Tris

Tris-LiCl, Tris-LiOH, Tris-LiOH-Orotate (across concentration and pH ranges)

Simulated Gastric Fluid (SGF)

Li+ electrode cannot function at low pH (~2.0) of SGF, so need to neutralize mixtures with sodium bicarbonate (NaCH0₃). Assay free Li+ when added before or after neutralization.

Measure at 37° C, across concentration ranges:

SGF-LiCl -> + NaHC0₃, SGF-Tris-LiOr -> + NaHC0₃, SGF -> + NaHC0₃ + LiCl, SGF -> + NaHC03 + Tris-LiOr

Rat plasma

Blood taken from terminal cardiac puncture, heparinized, plasma separated and frozen at -20° C.

Measure at 37° C, across concentration ranges:

plasma-LiCl, plasma-Li₂CO₃, plasma-LiOr

Artificial Urine (AU)

Artificial urine prepared according to DIN EN 1616:1999, from Pickering Laboratories (Mountain View, USA).

Measure at 37° C, across concentration ranges:

AU-LiCl, AU-Li₂CO₃, AU-LiOr