Lithium carbonate assays

An example of this type of calculation is the assay of Lithium Carbonate Tablets BP. Lithium carbonate is used as an antidepressant in 250 mg and 400 mg strengths. The BP assay is to weigh and powder 20 tablets. Add a quantity of the powder containing 1 g of lithium carbonate to 100 mL of water add 50 mL of 1 M hydrochloric acid and boil for 1 minute to remove carbon dioxide. Cool and titrate the excess acid with 1 m sodium hydroxide solution using methyl orange as indicator. The assay is then repeated omitting the sample. 

The calculation of the content of resorcinol in the solution is identical to the back titration method explained above for lithium carbonate. Consequently, the volume of added bromate is modified by the bromate factor and the thiosulfate titre volume is modified by the thiosulfate factor. A blank titration is not required for this assay since no heating or cooling of the reaction is involved. 

Q6.1 Lithium carbonate (Li2COs, Mr = 73.9) is a drug widely used in the treatment of depression. The BP assay for lithium carbonate involves the addition of an excess of hydrochloric acid to a sample of the drug and back titration of the un reacted hydrochloric acid with sodium hydroxide. 

ButyUithium is available as a 15—20 wt % solution in //-pentane or heptane. Noticeable decomposition occurs after alb reflux in heptane (bp 98.4°C) but not after a 15 min reflux in ben2ene (bp 80.1°C) or hexane (bp 68°C). /-ButyUithium in pentane or heptane is more stable than //-butyUithium in hexane (125). Solutions of /-butyUithium in pentane and heptane are flammable Hquids and are considered pyrophoric. The /-butyl compound is more reactive than either the n- and sec-huty. Di-//-butylether is cleaved by /-butyUithium in 4—5 h at 25°C, compared to the 2 d for j iZ-butyUithium and 32 d for //-butyUithium (126). /-ButyUithium can be assayed by aU of the techniques used for //-butyUithium. /-ButyUithium is a useful reagent in syntheses where the high reactivity of the carbon—lithium bond and smaU si2e of the lithium atom promote the synthesis of stericaUy hindered compounds, eg,... 

Oxalate does not interfere with glucose assays, but insulin values determined in oxalate-plasma are lower than those obtained with lithium heparin-plasma or serum (L6). Specimens collected in EDTA demonstrate lower carbon dioxide combining power than those observed with serum or heparin or potassium oxalate plasma (Zl). 

For the preparation of MIPM, the above phenol, 2,5-dimethoxyphenol was isopropylated with isopropyl bromide in methanolic KOH giving 2,5-dimethoxy-l-(i)-propoxybenzene as an oil. This formed the benzaldehyde with the standard Vilsmeier conditions, which melted at 77-78 °C from hexane and which gave a yellow malononitrile derivative melting at 171.5-173 °C. The nitrostyrene, from nitroethane in acetic acid was orange colored and melted at 100-101 °C from either methanol or hexane. This was reduced with lithium aluminum hydride in ether to give 2,5-dimethoxy-4-(i)-propoxyamphetamine hydrochloride (MIPM). The properties of the isolated salt were strange (soluble in acetone but not in water) and the microanalysis was low in the carbon value. The molecular structure had a pleasant appeal to it, with a complete reflection symmetry shown by the atoms of the amphetamine side chain and the isopropoxy side chain. But the nature of the actual product in hand had no appeal at all, and no assay was ever started. 

A solution of 110 mg. (0.83 mmoles) of 5ab in ether was added slowly to a solution of methyllithium (10% excess, Foote Chemical) in ether. The highly exothermic reaction was cooled in a room temperature water bath. Methane (39 ml.), ether vapor, and possibly carbon dioxide were collected [theoretical for proton abstraction reduction 19 ml. of methane]. After addition of ozonide was complete, the reaction was worked up in the same manner as the lithium aluminum hydride reduction. GPC analysis of the crude mixture revealed isopropyl alcohol (9) (>—60% by GPC standard) and 3-methyl-2-butanol (10) —60%). Methanol is normally produced in approximately the same yield (—60% ) as 9 and 10. We were unable to collect a sufiicient quantity from the labeling experiment for mass spectral analysis. Product identification was based on GPC retention times and by comparison of infrared spectra with those of authentic compounds. Mass spectral results were as follows isopropyl alcohol- assay 11.88% oxygen-18 3-methyl-2-butanol (10) assay 2.45%. 

The official methods are not consistent. In the B.P. about 0 2 g is dissolved in 40 ml of dimethylformamide and titrated with OTN lithium methoxide using quinaldine red as indicator precautions are taken against the effect of carbon dioxide and a blank is determined with the lithium methoxide. The B.P.C. uses considerably less solvent, 15 ml, for about 0 4 g of substance, thus providing a more suitable titration volume, but requires no protection against carbon dioxide. The latter conditions are in keeping with the findings of Ryan et al Prior neutralisation of the titration system as given under the Appendix on non-aqueous titration should always be carried out. However, in our opinion, the conditions for titration of barbitones by non-aqueous methods are so critical that as an assay for determination of purity they are not justified. 

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