3

Ca(OH), added, and the flask shaken during half an hour. The liquid is then filtered, and 40 c.c. (= 4 Gm. of opium) is taken for extraction with three successive portions, each of 40 c.c., of C,H,CH,. The C,H,CH, is filtered through a dry filter into a distillation flask, as before, each portion of CН¿CH ̧ being put through the filter immediately after extraction. In this way the final filtration is of the C,H,CH, least concentrated in codeine. Finally the filter paper is washed with a small amount of C.H,CH,. The C,H,CH, is concentrated to a small bulk (about 25 c.c.), as before, and dry HCl gas passed through it for half a minute. The C,H,CH, is filtered off, the codeine hydrochloride dissolved in water, and the solution filtered into a small weighed round-bottomed glass dish. The liquid is evaporated almost to dryness in a glass dish and now develops practically no colour. When only a small amount of water is left, a little weak EtOH is added to encourage crystallization, and rosettes of almost colourless crystals of codeine hydrochloride are obtained. The dish is dried to constant weight in the water oven and weighed, and the residue taken as C18H22NO2HCl + 11H2O. (See also Y.B., 1921, 6; 1922, 16.)

3

Codeine Hydrochloride, Solubility of. D. C. Wilson. (Pharm. J., 1923, [4], 56, 363.) The solubility of codeine hydrochloride is usually given as 1 in 20 at ordinary temperatures, but a re-determination of the solubility at 15.5° C. gave as the average of a number of closely agreeing results the value 1 in 28.5.

Delphinium Andersonii, Alkaloid Assay of. M. R. Miller. (J. Amer. Pharm. Assoc., 1923, 12, 492.) Delphinium Andersonii, one of the low larkspurs, so named from its habit of growth in distinction to the tall larkspurs as represented by D. glaucescens, is found in abundance in certain areas of Nevada, and has been found to be responsible for cattle losses under certain conditions. The roots of this species have been reported harmless when fed to sheep but the above-ground parts have been found, at the Nevada Agricultural Station, to be toxic to cattle. As there was not sufficient material available for the preparation of the alkaloids, alkaloidal assays were made on the air-dried leaves and stems before flowering. The method of assay was that employed by Beath. Twenty-five Gm. of the powdered material was extracted with EtOH 90 per cent. The percolate

4

was concentrated to one-third under reduced pressure, then further evaporated in a current of air. The aqueous residue thus obtained was shaken out with petroleum ether, then made alkaline with NH,OH and shaken out with CHCI,. The CHCI, was distilled off and the residue taken up with N/50 H2SO. The excess of H2SO, was then titrated with N/50 KOH and the acid found to be combined with the alkaloid was calculated as equivalent to delphinine C31H49O7N. Three samples gave from 1-9 to 1.75 per cent. of alkaloids. By the U.S.P. method for alkaloidal assay the result was 1.64 per cent. The author found cochineal to be a more satisfactory indicator than lacmoid, as used by Beath. (See also Y.B., 1919, 12.)

Echinopsine. Ernst Spaeth and Alfred Kolbe. (Monatsh., 1923, 43, 469-75, through Chem. Abstr., 1923, 17, 1478.) Echinopsine is a poisonous alkaloid found in different plants of the Echinops family. Greshoff gave it the formula C1,H,NO; it should be, however, C1,H,NO. The behaviour of this compound upon reduction with Na and EtOH, and upon heating with PC1, and direct comparison proved it to be 1-methyl-4-quinoline. (See also Y.B., 1909, 127 ; 1907, 52 ; 1921, 135 and Gen. Index.)

5

Hydrastine and its Hydrochloride, Melting Points of. D. B. Dott. (Pharm. J., 1922, [4], 55, 607.) The melting-point of hydrastine is generally given as 132° C., and that figure closely agrees with what is found in the case of the alkaloid as usually supplied. When this substance is exposed in the water-bath, there is no loss of weight beyond what may be due to traces of moisture. On further heating at 130° C.-135° C., the alkaloid melts and becomes coloured, but there is no perceptible loss of weight. The m.p. of the fused substance is found to be several degrees higher than originally observed. But the point to be specially noted is that when the alkaloid is converted into a salt and NH OH added to its solution, the base so obtained melts at 144° C.-145° C. Some of the precipitated hydrastine was crystallized from EtOH, and the crystals dried and powdered. The m.p. was 145° C.

Hydrastine hydrochloride is stated to melt at 116° C. The air-dry salt was found to have a somewhat indefinite and variable m.p., according to its method of preparation, but decidedly lower than 116° C. A definite result can only be obtained with the salt dried near 100° C. It is then found to melt at 168° C.,

with some decomposition. The published information on the subject is evidently misleading.

Hyoscyamine and its Sulphate, Action of Heat on. A. Goris and P. Costy. (Bull. Sci. Pharm., 1922, 29, 113.) The authors have previously shown that in the preparation of belladonna extract hyoscyamine is transformed into the less therapeutically active atropine. In order to investigate the action of heat on hyoscyamine, the authors have, with considerable difficulty, obtained that base in a state of practical purity. Advantage was taken of the difference of the solubility of the two bases in benzin: 100 Gm. of which dissolves 9.211 Gm. of atropine at 15° C. but only 0.920 Gm. of hyoscyamine. The ap of this purified hyoscyamine was -20°72 in absolute EtOH; 21°89 in EtOH 50 per cent.; both in 4 per cent. solutions: and - 23°43 in EtOH 20 per cent., the last in 1: 100 solution. The ap increases as the strength of the EtOH decreases. The anhydrous sulphate, prepared from this pure hyoscyamine, had the 27°40 or ad 26° for the salt with 2 mols. H2O. An even purer anhydrous sulphate, obtained by neutralizing an acetone solution of the base had the ap- 28°26. Also taking advantage of the different solubilities of the two sulphates in cold absolute EtOH, that of hyoscyamine sulphate being only 2-36: 100 at 15° C. and that of atropine sulphate 34.93: 100, a hyoscyamine sulphate was ultimately obtained having the ap - 28°03 in aqueous solution. Similar results were obtained by recrystallizing the hyoscyamine sulphate several times from absolute EtOH. It was found that pure hyoscyamine alone is only very slightly altered by 3 hours exposure to 100° C. But if the base is first dissolved in CHC1, before exposing it to this temperature, considerable change occurs and the falls from ad 21°89 to 14°10. At 106° C., the ap of the alkaloid falls to 17°03 in 1 hour, to 15°22 in 2 hours, and to 13°30 in 4 hours. At 118° C. the alteration is even more marked. A similar but less pronounced change occurs when the base is heated in solution in absolute EtOH. In presence of water, in an autoclave the base is much affected at 100° C. and at 109° C. it is all transformed into atropine. The sulphate is relatively stable in aqueous solution. The experiments show that pure hyoscyamine has the ap 22° for a 4100 solution in EtOH 50 per cent. and the sulphate the ap 28° 26°50 for the hydrated salt with 2 mols. H2O. In commercial samples a tolerance of

-

10 per cent. on these figures is permissible. Hyoscyamine appears to be a fairly stable base and is not racemized as quickly as has been supposed at 100° C.; but it is rapidly transformed into atropine at slightly higher temperatures.

2

Ipecacuanha, Determination of Total Alkaloids in. G. From me. (Pharm. Zentral, 1923, 64, 167.) Six Gm. of the finely-powdered root in a tared stoppered flask is macerated, with frequent shaking, with 60 Gm. of Et2O and 5 Gm. of NH ̧OH, 10 per cent. After standing, a known weight of the clear Et2O extract is decanted into a flask, and the solvent distilled off. The residue is then taken with 10 c.c. of EtOH, and 40 c.c. of water and titrated with N/10 HCl with methyl red indicator. Or the residue may be redissolved in N/10 HCl, the solution made alkaline in a separator with NH OH and shaken out with Et,O. The solvent is then distilled off, and the dry residue weighed.

Morphine, Detection of Apomorphine in. W. Kraut. (Apoth. Zeit., 1921, 13, 124, through Bull. Sci. Pharm., 1923, 30, 426.) Five c.c. of a 1:30 solution of morphine hydrochloride is treated with a few drops of NaOH solution, until alkaline in reaction, and then shaken in contact with the air with 1 c.c. of CHCI,. No trace of a bluish tint should be evident in the CHCl, and the aqueous portion should show no reddish violet tinge. On adding a drop of KHCO, to the morphine hydrochloride solution, and heating to boiling, no colour should be produced. It is claimed that these tests will detect 0.02 per cent. of apomorphine in morphine hydrochloride.

Morphine, Determination of. J. R. Nicholls. (Analyst, 1922, 47, 506.) Extraction. To one volume of morphine solution (from which if necessary other alkaloids have been removed by means of Et2O or CHC1, from the solution made alkaline with NaOH, KOH or Ca(OH)2), add one volume of EtOH, make the liquid ammoniacal and shake it with one volume of CHC13. After running off the separated lower layer, add half a volume of EtOH and shake with one volume of CHCI,. Separate and repeat the process for a third extraction; if the quantity of morphine exceeds 0.1 Gm., a fourth extraction should be made. Evaporate the combined extracts on the steam bath, dissolve the residue in standard acid, make up to definite volume, and estimate the morphine as described below.

1. Titration. A large aliquot portion of the filtered liquid is titrated with standard alkali, with methyl red as indicator (slightly low results are given with methyl orange or cochineal), and the corrected difference figure calculated to morphine.

2. Colorimetric Estimation. The method used is that of Georges. A portion of the acid solution is diluted so that it contains not more than 4 Mgm. of morphine per 10 c.c. One drop each of N/H2SO, and saturated KIO, solution is added for every 1 c.c. of solution taken, and after 5 minutes, 1 drop of strong NH4OH solution for every 1 c.c. of solution is added and the colour compared, after 2 minutes, with a series of standards made up at the same time. The limiting dilution is about 1 in 30,000.

3. Polarimetric Estimation. Part of the filtered acid solution is read polarimetrically. By the use of white light with a saccharometer, the rotation of anhydrous morphine in dilute H2SO at 20° C. was found to be [a], 140°, and was independent of variation in the quantity of excess acid.

With quantities of morphine greater than 10 Mgm. the titration figure with N/50 solutions is by far the most accurate. The colorimetric estimation is very useful for small quantities of morphine and as a check on the titration, but it is hardly possible to avoid an error as great as ±2 per cent. of the actual morphine. The polarimetric reading is usually so small that the experimental error is considerably greater. It forms, however, a rapid check on the titration figure when a moderate amount of morphine is present.

The above-described general method can be employed for the estimation of heroin and similar derivatives of morphine. The base is extracted by Et2O or CHCl,, hydrolyzed with weak KOH solution to morphine, and the latter extracted and estimated.

Morphine and the Secondary Alkaloids, Determination of, in Opium and its Galenical Preparations. M. A. Mancini. (Boll. chim.farm., 1923, 62, 3, 35, 69, 101, through Chem. Abstracts, 1923, 17, 2344.) From comparative studies of the various methods for the determination of morphine the author considers that of the U.S.P. the best, and next in the order of preference the method of the French Codex and that of Tingle. For the determination of the secondary alkaloids in opium and its pre