Abstract
Introduction
Experiment
Results and discussions
Acknowledgement
Author: V. S. RAMANATHAN, J. C. PAL, C. RAMACHANDRAN,
Pages: 25 to 29
Creation Date: 1966/01/01
The narcotine content of the opium produced in two seasons in each of the districts of Uttar Pradesh, Madhya Pradesh and Rajasthan in India has been reported. Opium collected in the first lancing and subsequent lancing was separately analysed for narcotine. Indian opium has a narcotine content ranging from 5.62 percent to 7.68 percent. Opium produced in Madhya Pradesh and Rajasthan has a higher percentage of narcotine than the opium of Uttar Pradesh. Narcotine percent in opium marc, crude narcotine and technical narcotine has also been worked out.
Next to morphine, narcotine is the second most abundant alkaloid present in opium. It was used as a prophylactic the treatment of malaria (1) and was later discarded as an anti-malarial drug. Recent researches have shown its use as an antitussive drug (2 to 12). It is claimed in literature that narcotine is not only nonnarcotic and non-addictive but also is non-toxic and has no ill effects on blood pressure and respiration. As a cough remedy it is stated to be more effective than codeine, particularly in children. Narcotine therefore has gained considerable importance in the recent past and its use in medicine has gone up. It finds a place in the latest editions of B.P., B.P.C., U.S.P., N.F. XII and J. P. Cotarnine Chloride B.P.C., a styptic (13) and narceine (14 to 16), another natural alkaloid of opium used as an antispasmodic, are synthetically prepared from narcotine.
Various methods of estimating narcotine have been published (17 to 25). Russian scientists (23, 24), by their method of estimation, reported that their opium contained as high as 12 percent narcotine and suggested that Russian opium is closest to Indian opium. This Figures in parentheses refer to references, p. 29. created an interest to know the narcotine content in authentic samples of opium grown in the various districts of India. The demand for narcotine for medicinal purposes in India is also steadily increasing. Hence the present investigation to study the narcotine in Indian opium was undertaken.
Note. Figures in parentheses refer to references, p. 29.
Samples drawn from raw good opium received from the District Opium Officers, produced in each of the districts of Uttar Pradesh, Madhya Pradesh and Rajasthan for the seasons 1962/63 and 1963/64 were composited, representing one sample for each district for each season separately for opium of first lancing and subsequent lancing. The composited samples of opium were dried at 70°C, powdered, sieved and stored in airtight bottles.
Dry powdered opium (4.65 g) was well triturated in a glass mortar with hydrochloric acid (45 ml of 3 % v/v) added slowly from a burette in portions of 5 ml first and then 10 ml each 4 times, which facilitated easy working and thorough extraction. It was then filtered and 30 ml of the filtrate representing 3 g of opium were pipetted in a beaker (100 ml), heated to 70°C on a steam bath to which hot alcohol (20 ml, 95%) was added. Narcotine was precipitated from the hot solution by the addition of powdered potassium bicarbonate under stirring until the pH was about 6, as determined by Universal Indicator. The pH was finally adjusted with potassium bicarbonate exactly to 7 using Cambridge Ph meter. The beaker with contents was kept in an ice bath for an hour. The precipitated narcotine was filtered through a Hirsch funnel fitted to a Buchner flask using Edwards vacuum pump. It was then washed with cold dilute alcohol (35 percent, v/v, 5 ml, 5 times), with water (5ml, once) and with 1 percent caustic soda solution (10 ml, twice) and finally with water till free from alkali.
Season to which the opium belongs |
||||||
---|---|---|---|---|---|---|
1962-63 % narcotine on dry matter |
1963-64 % narcotine on dry matter |
|||||
Serial No.
|
Name of State
|
Name of district and lancing
|
By
weighment
|
By
titration
|
By
weighment
|
By
titration
|
1 |
Uttar Pradesh
|
Faizabad (lst lancing)
|
6.61 | 6.51 | 6.26 | 6.28 |
2 |
Uttar Pradesh
|
Faizabad (Subsequent lancing)
|
5.95 | 6.20 | 5.75 | 5.79 |
3 |
Uttar Pradesh
|
Bareilly (lst lancing)
|
6.65 | 5.72 | 5.73 | 5.62 |
4 |
Uttar Pradesh
|
Bareilly (Subsequent lancing)
|
6.49 | 6.42 | 5.94 | 5.86 |
5 |
Uttar Pradesh
|
Barabanki (1st lancing)
|
6.12 | 6.00 | 6.22 | 6.14 |
6 |
Uttar Pradesh
|
Barabanki (Subsequent lancing)
|
5.71 | 5.69 | 5.71 | 5.86 |
7 |
Uttar Pradesh
|
Shahjahanpur (lst lancing)
|
6.96 | 6.91 | 6.79 | 6.70 |
8 |
Uttar Pradesh
|
Shahjahanpur (Subsequent lancing)
|
6.20 | 6.24 | 6.49 | 6.49 |
Average for Uttar Pradesh
|
6.21 | 6.21 | 6.11 | 6.09 | ||
9 |
Madhya Pradesh
|
Ratlam (lst lancing)
|
7.27 | 7.14 | 7.68 | 7.47 |
10 |
Madhya Pradesh
|
Ratlam (Subsequent lancing)
|
7.20 | 6.92 | 7.40 | 7.20 |
11 |
Madhya Pradesh
|
Neemuch
|
6.68 | 7.04 |
-
|
-
|
12 |
Madhya Pradesh
|
Mandsaur
|
6.81 | 6.95 |
-
|
-
|
Average for Madhya Pradesh
|
6.99 | 7.01 | ||||
13 |
Rajasthan
|
Kotah (lst lancing)
|
6.70 | 6.75 | 6.30 | 6.27 |
14 |
Rajasthan
|
Kotah (Subsequent lancing)
|
6.09 | 6.19 | 6.17 | 6.02 |
15 |
Rajasthan
|
Jhalawar (lst lancing)
|
6.10 | 6.19 | 6.40 | 6.40 |
16 |
Rajasthan
|
Jhalawar (Subsequent lancing)
|
6.48 | 6.65 | 6.27 | 6.20 |
17 |
Rajasthan
|
Chittorgarh
|
6.63 | 6.86 | 7.11 | 7.19 |
18 |
Rajasthan
|
Pratabgarh (lst lancing)
|
6.69 | 6.69 | 6.68 | 6.89 |
19 |
Rajasthan
|
Pratabgarh (Subsequent lancing)
|
-
|
-
|
6.66 | 6.61 |
Average for Rajasthan
|
6.44 | 6.55 | 6.51 | 6.51 |
The precipitate was dried at 100°C and without removing from the Hirsh funnel was dissolved with warm acetone (10 ml) and the solution filtered into a tarred conical flask (100 ml) followed by washing the funnel with warm acetone (10 ml, 4 times). Acetone being a low boiling solvent no suction was applied during filtration.
The solvent was distilled off and the residue dried and weighed. The residue was then dissolved in glacial acetic acid (10 ml) and acetic anhydride (5 ml) and titrated with 0.1 N solution of perchloric acid in glacial acetic acid using crystal violet as indicator, the colour change taking place from violet to green through bluish green.
1 ml of 0.1 N perchloric acid was equivalent to 0.04134 g of narcotine. In the above method the following modifications have been made over the published procedure:
i) The pH of the solution was exactly maintained at 7 by using a pH meter for the precipitation of narcotine.
ii) Filtration of the solution in a Hirsch funnel was quicker than through sintered glass funnel.
iii) The percent narcotine obtained by weighment is practically the same as that obtained by titration with perchloric acid.
iv) Standardisation of perchloric acid was done with potassium biphthalate (British Drug Houses) dissolved in glacial acetic acid. The results of analysis are reported in Table 1.
The purity of the narcotine obtained was examined and it was found to be free from morphine and other alkaloids.
In the Gregory-Robertson 26 process adopted in the manufacture of opium alkaloids, the raw opium is first extracted with water at pH 5.5 and almost the whole quantity of narcotine in the opium remains undissolved and is removed along with the opium marc. [ 27] The opium marc thus obtained is then steeped in water and extracted with sulphuric acid at pH 2 to 3 at a temperature of 60-70°C. The acid extract was filtered from the insoluble opium wax and resins and the filtrate made alkaline with sodium carbonate to precipitate the crude narcotine. The crude narcotine was filtered, washed with water and dried. It was a dark brown solid.
The sample of opium marc was dried at 100°C in an air oven, powdered, sieved and stored in air-tight bottles. Opium marc obtained from good opium was in a fine powdered condition whereas that obtained from adulterated opium was sticky and soft to the feel due to the foreign substances present in it. In the good opium marc, estimation of narcotine was done by extracting the sample (4.65 g) with hydrochloric acid (45 ml of 3% v/v) and precipitating the narcotine from aliquot part (30 ml) with potassium bicarbonate following the method described for opium.
The method of estimation of narcotine in adulterated opium marc was slightly modified. Adulterated opium marc (4.65 g) was triturated with hydrochloric acid (45 ml of 3 % v/v added in portions of 5 ml first and 10 ml, 4 times) and purified sand (1 g) and kept soaked in acid for 2 hours with occasional grinding at intervals of 5 minutes. The inert material sand was added to facilitate the easy grinding of the plastic marc. It was then filtered and the estimation of narcotine in the filtrate (30 ml) was determined by the method described for opium.
Serial No.
|
Name of the region of opium
|
Percentage of narcotine on dry matter
|
1 |
Madhya Pradesh and Rajasthan (Malwa opium)
|
13.46 |
2 |
Madhya Pradesh and Rajasthan (Malwa opium)
|
13.86 |
3 |
Uttar Pradesh (Banaras opium)
|
11.15 |
4 |
Uttar Pradesh (Banaras opium)
|
10.92 |
5 |
Adulterated opium marc
|
11.05 |
6 |
Adulterated opium marc
|
10.72 |
Estimation of narcotine in crude narcotine by the method described above did not give satisfactory results, as the percentage of narcotine obtained in them was found to be lower. Hence the method of estimation was modified to give correct results. Dry powdered crude narcotine (1 g) was extracted in a glass soxhlet with acetone for 4 hours until the acetone extract was no more coloured. The acetone was then distilled off to reduce the bulk, transferred to a dish and evaporated to dryness on a steam bath. The dry residue was extracted with hydrochloric acid (3 % v/v, 5 ml, 5 times), warmed on a steam bath and filtered through a plug of cotton. The insoluble resins and residues on the cotton plug were washed with water (5 ml, 2 times). The narcotine in the clear filtrate was then precipitated with potassium bicarbonate at pH 7 and estimated by titration adopting the method described for opium. The percentage of narcotine in crude narcotine in the samples analysed is given in Table 3.
Serial No.
|
Region of opium
|
Percentage narcotine on dry matter
|
1 |
Malwa
|
30.13 |
2 |
Malwa
|
38.76 |
3 |
Malwa
|
32.89 |
4 |
Malwa
|
35.30 |
5 |
Malwa
|
31.82 |
6 |
Banaras
|
25.32 |
7 |
Banaras
|
26.47 |
8 |
Banaras
|
25.02 |
9 |
Banaras
|
22.86 |
10 |
Banaras
|
22.81 |
Crude narcotine was extracted with benzene and the benzene extract distilled off to obtain the technical grade of narcotine. It was a dull white powder (melting point 170-172°C) with 95-97 per cent narcotine. For the estimation of narcotine, technical grade of narcotine (0.5 g) was dissolved in hydrochloric acid (3 percent, 10 ml) and filtered. It was then washed with water (20 ml). The narcotine in the filtrate was precipitated with potassium bicarbonate and the percentage determined by titration following the procedure described for opium. The results obtained are shown in Table 4 .
Serial No.
|
Loss on drying at 105°C (3 hours)
|
Residue on ignition
|
Narcotine on dry matter
|
1 |
0. 10
|
0.38 | 96.54 |
3 | 0.59 | 0.52 | 95.28 |
3 | 0.18 | 0.62 | 95.57 |
4 | 0.10 | 0.25 | 97.50 |
The residues obtained after the extraction of crude narcotine with benzene contained less than one per cent narcotine and its estimation as given under opium did not give satisfactory results. Hence the dry powdered residue (5 g) was extracted with acetone in a glass soxhlet for six hours and the estimation completed by following the procedure described above for crude narcotine. The results obtained are given in Table 5.
Serial No.
|
Narcotine on dry matter
|
1 | 0.20 |
2 | 0.36 |
3 | 0.50 |
4 | 0.32 |
Noscapine B.P., U.S.P.
The purified narcotine was a white crystalline powder m.p. 175-176°C. It satisfied the assay and other specifica- tions of the Pharmacopoeias of various countries for Noscapine (narcotine). The noscapine hydrochloride prepared from this conformed to the specifications laid down in the latest edition of J.P. and N.F. XII of U.S.A. Narceine prepared from narcotine using p-methyl toluene sulphonate as the methylating agent had m.p. 171°C (Lit (28).m.p. 170-171°C).
From the results in Table 1 it may be seen that Indian opium contains 5.62 to 7.68 per cent of narcotine. The narcotine content the opium grown in Uttar Pradesh, Madhya Pradesh and Rajasthan is not the same. Opium originating from Madhya Pradesh has higher narcotine than the opium from other regions in India. Opium of first and subsequent lancing has practically the same narcotine content. The narcotine content in opium marc and crude narcotine in Tables 2 and 3 also confirms that Malwa opium has a higher narcotine content than Banaras opium. Indian opium has a lower narcotine content than Russian opium. Indian opium has a much higher percentage of narcotine than the opium of Yugoslavia (29), Turkey (29) and that obtained from the "Ikkanshu" variety of opium poppy cultivated for actual production of opium in Japan [ 30] . According to the geographical origin of opium, the codeine and narcotine content in opium generally increases from the Macedonian region in the West, as we proceed towards the East. Narcotine being a weakly basic alkaloid remains insoluble during extraction of opium with water at pH 5.5. Some of the resins and colouring matters in the opium marc being amphoteric in nature are soluble in acidic solution and they are reprecipitated along with narcotine when made alkaline. Hence the crude narcotine obtained from opium marc contained much resins, gums and other impurities and it was found not possible to purify the crude narcotine without adopting solvent extraction. The narcotine content in the crude narcotine varied from batch to batch, depending upon the quality of the opium marc used, temperature of extraction and the pH of the acid extract.
The authors are indebted to the Government of India, Ministry of Finance, Department of Revenue, New Delhi, for permission to conduct this investigation and to publish the results.
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