Indian Journal of Chemical Technology Vol. 10, July 2003, pp. 355-362

Articles

New titrimetric and spectrophotometric methods for the determination of promethazine theoclate using metavanadate

K Basava iah * & V S Charan

Department of Chemistry, University of Mysore, Manasagangotri , Mysore 570 006, India

Received I April 2002; revised received 31 December 2002; accepted 10 Apri/2003

Four new methods (titrimetric and spectrophotometric, two each) which are accurate, precise and rapid are described for the determination of promethazine theoclate in bulk form and in tablets. The titrimetric methods are based on the oxidation of the drug by metavanadate in acidic condition followed by determination of the unreacted oxidant by titration with iron(II) ammonium sulphate (Method A) or titration of the vanadium(IV) formed, with cerium(IV) sulphate (Method B). The spectrophotometric procedures are also based on the oxidation of the drug with metavanadate followed by the estimation of unreacted oxidant after complexing with chromotropic acid and measuring the absorbance at 420 DID (Method C) or estimation of the vanadium(IV) formed, by reacting it with ferriin and measuring the resulting ferroin at 510 DID (Method D). Method A and Method B are applicable over the ranges 1-20 and 5-12 mg, respectively. Calculations in both methods are based on the reaction stoichiometry of 1:2 (drug: metavanadate). In spectrophotometry, Beer's law is obeyed over the ranges 0.0-125.0 and 10.0-60.0 J.l.g mL"1

for method C and method D, respectively and the corresponding molar ab'Sorptivity values are 2.64x103 and 5.33x103

L mor1 cm·I, respec.tively. The methods were successfully applied to the determination of promethazine theoclate in avomine tablets, and the results obtained were in the range of 97.73-102.24% of declared content with a relative standard deviation of 1.51-2.22%.

Promethazine theoclate (PMT) is an antihistamine H 1

receptor antagonist. It is primarily an antihistamine with additional sedative and antiemetic actions. PMT is used in the treatment of nausea and vomiting associated with migraine labyrinthine disorders and radiation therapy. Not many methods are found in the literature for the determination of PMT. Davidson 1

has determined the drug in tablets by difference spectrophotometric method. A condensation reaction involving PMT and formaldehyde in strong H2S04

medium at 4-5°C and subsequent measurement at 551 nm has also been reported2

. Recently a flow-injection method with cerium(IV) oxidation of the drug and measurement of the coloured radical cation has been described by Martinez and Garcia3

.

In the present work, a combination of redox property and complexing ability of metavanadate has been exploited for developing four procedures for the determination of PMT. In two methods (A and C), the drug is oxidized by a known excess of metavanadate and after the reaction is judged to be complete, the unreacted oxidant is either backtitrated (A) or determined by spectrophotometry by complexing with

*For correspondence (E-mail: basavaiahk @yahoo.co.in ; Fax: 0091 -82 1-42 1263)

chromotropic acid (C). In the pther two procedures (Methods B and D), a large excess of metavanadate is employed to oxidize PMT, and the reduced form of the oxidant vanadium(IV), is determined either by titrimetry with cerium(IV) or by spectrophotometry by reacting the vanadium(!\') with ferriin. The spectrophotometric procedures are based on reactions at room temperature compared to 4-5°C required in the reported procedure2

, and use a si mple spectrophotometer for measurement, whereas the flow injection method involves an expensive experimental set-up which is not always easily available. Both procedures employ mild working conditions and are based on measurement of coloured species which are stable for several months unlike the unstable condensation product2 or radical cation3

. The additional advantage is the long and dynamic concentration ranges of applicability in comparison with narrow ranges of 10.0-60.0 and 10.3-31.3 J.,lg mL·' for reported methods2.3 .

Experimental Procedure Apparatus

A Systronic model 106 digital spectrophotometer provided with 1-cm matched glass cells was used for absorbance measurements.

Articles

Reagents and solutions All chemicals used were of analytical reagent grade

and double distilled water was used throughout the study. A 0.05 M sodium metavanadate solution was prepared by dissolving - 3 g of reagent (S.D. Fine Chern. Ltd. India) in water and diluting to 500 mL and standardized using iron(II) ammonium sulphate4. After standardization, the solution was diluted to 0.02 M and 250 ~J.g mL·' for use in titrimetry (Method A) and spectrophotometry (Method C), respectively. Cerium(IV) sulphate (0.05 M) was prepared by dissolving 20.2 g of the reagent (Loba-Chemi) in 0 .5 M H2S04 and diluting to 500 mL with the same acid and standardized using iron(II) solution4 . It was then diluted to get 0.02 M solution for use in titrimetric work (Method B). N-phenylanthranilic acid (NPA) indicator (0.1%) was prepared by dissolving the requisite amount in alcohol. Ferroin indicator was prepared by dissolving 1.485 g of 1,10-phenanthroline in 100 mL of 0.025 M ferrous sulphate.

Ferriin reagent was prepared by dissolving 0.16 g of iron(III) ammonium sulphate and 0.198 g of 1,10-phenanthroline base in 2 mL of 1 M HCI and diluting to 100 mL with water. Chromotropic acid reagent (0. 1%) was prepared by dissolving 0.1 g of acid in water and diluting to 100 mL. Aqueous solutions of HzS04 (10 M), CH3COOH (10 M), ammonia (1:1) and hydroxylammonium chloride (5%) were perpared in the usual way. AR grade acetone was used in titrimetric work (Method B) . Pharmaceutical grade PMT was procured from Rhone-Poulenc, India and used without further purification. A stock standard solution containing 2 mg mL·' of PMT was prepared by dissolving 200 mg of sample in a few drops of 0.1 M HCl and diluting to 100 mL with water. The solution was kept in an amber coloured bottle and stored in a refrigerator. This was diluted to get 500 and 250 !J.g mL-1 solution for spectrophotometric methods C and D, respectively.

General Methods Method A Reaction stoichiometry

The reaction stoichiometry was examined by allowing 1-20 mg of the sample dissolved in 0.1 M­HCl to react with a known amount of metavanadate solution. The reaction was allowed to proceed for 5 min, after which the excess of metavanadate was back-titrated with iron(ll) ammonium sulphate using NPA indicator. The value of n, the number of moles

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Indian J. Chern. Techno!., July 2003

of metavanadate required to react with each mole of drug was calculated using the equation,

volume of meta vanadate solution x

molarity of meta vanadate solution n=----~--------------------

volume of drug solution x

molarity of drug solution

and results obtained are presented in Table 1.

Method A 10 mL aliquot of drug solution containing 1-20

mg of PMT was pipetted into a 100 mL titration flask and was acidified by adding 5 mL of I 0 M H2S04. Then, 10 mL of 0.02 M metavanadate was added by means of a pipette, the contents were mixed well and kept aside with occasional shaking. After ensuring the complete oxidation of the drug as indicated by the complete disappearance of the red colour of the radical cation (5 min), the unreacted metavanadate was titrated with 0 .02 M iron(II) ammonium sulphate solution using 2 drops of NPA indicator. A blank titration was performed simultaneously, and the amount of the drug in the aliquot was calculated using the equation:

Amount(mg) = (B-S) x R x 249.5 ... (1)

where

B = volume of iron(II) solution used in the blank titration, mL

S = volume of iron(II) solution used in the sample titration, mL

R = molarity of iron(II) ammonium sulphate solution

Method B Reaction stoichiometry

Before applying the reaction to the quantitative determination of PMT, the stoichiometry of the reaction was determined by treating an aliquot of the drug solution containing 5-12 mg PMT with an unmeasured excess of metavanadate solution in acid conditions, and determining the amount of vanadium(IV) formed, by titration with cerium(IV) sulphate solution under the specified condition of indicator and catalyst. Then using the equation,

Basavaiah & Charan: Titrimetric and spectrophotometric methods for the determination of promethazine theoclate Articles

volume of cerium(IV) solution x

molarity of cerium(IV) solution n=----~--------~~------

volume of drug solution x

molarity of drug solution

the stoichiometry of the reaction was calculated and results are presented in Table 1.

Method A 10 mL aliquot of standard drug solution

equivalent to 5-12 mg of PMT was measured accurately into 100 mL conical flask followed by 2 mL of 10M H2S04. Then 10 mL of 0.05 M sodium metavanadate solution was added, the contents were mixed well and set aside for 5 min to ensure the complete oxidation of the drug. Finally 10 mL of acetone and 2 drops of ferroin indicator were added and the vanadium(IV) was titrated with cerium(IV) solution slowly near the equivalence point. The amount of drug in the aliquot was calculated using the equation:

Amount(mg) = V x R x 249.5

where

V = volume of cerium(IV) solution consumed R = molarity of cerium(TV) solution

Method C Varying aliquots (0.0 to 2.5 mL of 500 Jlg mL-1

) of PMT solution were measured accurately into a series of 10 mL standard flasks by means of a microburette. The volume was adjusted to 3 mL by adding water. Then, 1 mL of 10 M H2S04 and 2.5 mL of 250 Jlg mL- 1 metavanadate solution were added, the contents were mixed well and the flasks were allowed to stand for 20 min to facilitate the oxidation of the drug. Finally, 0.5 mL of 0.1 % chromotropic acid and 1 mL of 5% hydroxylammonium chloride were added, diluted to the mark with water, mixed well and absorbance of each solution was measured at 420 nm against water as blank.

MethodD Different aliquots of 250 Jlg tnL- 1 of standard PMT

solution in the range 0.4 to 2.5 mL were transferred into a series of 10 mL calibrated flasks and the total volume was adjusted to 3 mL by adding requisite

volume of water. Then, 0.5 mL each of 10M H2S04 and 0.05 M metavanadate were added to each flask , the contents were mixed well and set aside for about 5 min to allow the oxidation of the drug to complete as shown by the formation of colourless solution. Lastly, 2 mL each of 10 M acetic acid and ferriin reagent were added followed by 2 mL of I : 1 ammonia after 5 min and diluted to the mark. The absorbance of each solution was measured at 510 nm after a standing time of 10 min against water as blank.

For both spectrophotometric methods, a standard curve was prepared or a regression equation was evaluated. The concentration of the unknown solution was read from the calibration graph or computed from the regression equation.

Procedure for avo mine tablets Twenty tablets were weighed accurately and

ground to a fine powder. A portion of the powder equivalent to 200 mg of the active component was weighed accurately into a 100 mL standard flask, 60 mL of water and 5 mL of 0.1 mL HCl were added and shaken thoroughly for about 20 min . Then the volume was made up to the mark with water, mixed well and filtered using a quantitative filter paper. The first 10 mL portion of the filtrate was rejected and a suitable aliquot was then taken for analysis using the titrimetric procedures A and B. The filtrate was appropriately diluted to get 500 and 250 Jlg mL-1 for spectrophotometric procedures C and D, respectively , and a suitable aliquot was subjected to analysis as described under general methods.

Results and Discussion PMT being a N-substituted phenothiazine

derivative undergoes two-step oxidation, first to red coloured radical cation and then to colourless sulphoxide5 (Fig. 1) by metavanadate in H2S04 medium, and in the process metavanadate is reduced to vanadium(IV). The proposed methods are based on the determination of either unreacted metavanadate or vanadium(IV), the reduced form of vanadium(V).

Method A PMT was found to be oxidized quantitatively to its

sulphoxide by metavanadate in acid medium. The reaction was found to be slow in HCl and H3P04 media and was found to be rapid and quantitative in H2S04 medium. Under similar conditions of acid strength, the oxidation reaction took more than 30 min

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cx:D I R

PMT (colourless)

+

~SX) e~N I #

I R

0 I

H" + ~SX)'-":: ~ N #

I R

Sulphoxide (colourless)

~~~ ~if~

I R ! Radical cation (coloured}

(X~X) I R l H,O

OH

I

o=sX) I +W N ~

I R

Fig. !- Reaction scheme for oxidation of PMT.

in the case of HCI and the reaction was found to be incomplete even after 60 min when H3P04 was used. Both media gave non-stoichiometric results under the specified conditions of standing time (5 min). A 5 mL volume of I 0 M H2S04 in a total volume of about 25 mL was found to be adequate for both oxidation and backtitration steps. In the 1-20 mg range studied, 2 moles of vanadate were found to react with each mole of drug giving a stoichiometric ratio of 1:2 (PMT:oxidant ). A I 0 mL of 0.02 M meta vanadate was found suffi cient to cause oxidation of the drug in the studied range in a reasonable time of 5 min . Larger concentration of oxidant up to 0.05 M did not affect the stoichiometry and the results.

Method B Of the few titrimetric procedures6

-9 available for the

determination of vanadium(IY), one useful and convenient procedure9 involves the titration with cerium(IY) in H2S04 medium using ferroin indicator and in the presence of acetone catalyst. Method B is based on the oxidation of PMT to sulphoxide by a large excess of vanadate in acid medium and the titration of resulting vanadium(IY) with cerium(IV) as described by Sriramam et a /.9 For the oxidation of the drug as well as the titration of vanadium(IV), a 2 mL of I 0 M H2S04 in an overall volume of about 25-30 mL was found optimum. Even in this method, the drug and metavanadate were found to react in a I :2 molar ratio. A 10 mL of 0 .05 M metavanadate solution was found adequate to effect the oxidation of the drug in the 5-12 mg range. Contact times up to 30

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Indian J. Chern. Technol. , July 2003

min had no effect on either the sto ichiometry or the results of assay.

The relation between the drug amount and the titration end-point in both the methods was examined. The linearity between the two variables is apparent from the correlation coefficient of -0.9996 and 0.9985 for methods A and B, respectively, revealing that the reaction between PMT and metavanadate proceeds stoichiometrically in the ratio 1:2. In method B, the titration of vanadium(IV) should be performed slowly particularly towards the end-point with an interval of at least 20 s between two additions.

Method C In acidic solutions, chromotropic acid was found to

give a yellow coloured chromogen with metavanadate which is believed to be a complex 10

. Since metavanadate easi ly oxidizes PMT in acidic conditions, the colour reaction between metavanadate and chromotropic acid was used for the determinati on of PMT in ppm level.

In the present . study , a known amount of metavanadate was made to oxidize PMT to its sulphoxide in H2S04 medium and the unreacted oxidant was determined by complexing with chromotropic acid in the same acidic conditions employed to cause oxidation of the drug. PMT when added in increasing concentrations to a fixed concentration of metavanadate, consumes the latter and consequently there wi ll be a concomitant fall in the concentmtion of metavanadate. This is observed as a proportional decrease in the absorbance of the yellow colour with increasing concentration of PMT (Fig. 2). The decreasing absorbance values at 420 nm were plotted against increasing concentration of PMT to obtain the calibration graph (Fig. 3) .

By a preliminary study it was found that Beer's law is obeyed up to 750 Jlg mL-1 of sodi um metavanadate under the specified ac id and reagent concentrations (Fig. 4 ). Hence different amounts of PMT were reacted with a fixed concentration (750 Jlg m.L-1

) of the oxidant in the assay procedure. In this procedure two blanks were prepared. The reagent blank which contained the optimum concentration of all the reactants except PMT gave maximum absorbance. The other blank was prepared in the absence of metavanadate and PMT which showed negligible absorbance. Hence, all measurements were made against water. The yellow colour measured was found to be stable for several months.

Basavaiah & Charan: Titrimetric and spectrophotometric methods for the determination of promethazine theoclate Articles

0.5

0.4

.. 0.3 u

= • .c ... 0 2 .. .c 0.2 <

0.1

370 380 390 400 410 420 430 440 450 460 470 480 490 500

Wavelength, nm

Fig. 2-Absorption spectrum for method C. 1. Blank. 2. Solution with 75 J.l.g mL-1 of PMT + 1 mL of 10 M H2S04 + 2.5 mL of 250 J.l.g mL·1 NaV03 + 0.5 mL of 0. 1% chromotropic acid + I mL of 5% hydroxylammonium chloride diluted to 10 mL

0.6 ·r--------------------,

~ .. ..

0.5

0.4 -

-e 0.3 -a .c <

0.2

0. 1

0¥-----.-----.-------.------i 0 2 3 4

Volume of metavanadate, mL

Fig. 4-----Calibration curve for vanadate by chromotropic acid. ( I mL of I 0 M H2S04 + 0.5 mL of 0. I% chromotropic acid + I mL of 5% hydroxylammonium chloride).

Since the oxidation of PMT by vanadium(V) was slow in HCl and H3P04 medium, H2S04 was chosen as the reaction medium for the oxidation step. A 1 mL volume of 10 M H2S04 in an overall volume of 6.5 mL was found adequate for the oxidation step. The same quantity of acid in a total volume of 10 mL (1 M HzS04) was used for the determination of unreacted metavanadate with chromotropic acid although the latter reaction was found to be unaffected in 0.1 to 2.0 M H2S04 concentration. Further, 0.5 mL of 0 .1% chromotropic acid and 1 mL of 5% hydroxylammonium chloride solution were sufficient to determine the unreacted metavanadate.

0.4

.. ;$ 0.3 .. -e Cl

~ 0.2

0 .1

0 0.5 1.5 2 2.5 3 Volume of PMT, mL

Fig. 3--Calibration curve of method C (0.0 to 2.5 mL of 500 J.l.g mL- 1 of PMT+l mL of 10M H2S04 + 2.5 mL of 250 J.l.g mL-1

NaV03 + 0.5 mL of 0.1 % chromotropic acid + I mL of 5% hydroxylammonium chloride diluted to 10 mL).

0.5

0.4

t 0.3

li -e ~ 0.2 <

0.1

420 430 440 4l0 460 470 4&0 490 lOO liO l lO l30 l40 l lO l 60

Wavelenctb, nm

Fig. 5--Absorption spectrum for method D. I. 50 J.l.g mL·1 of PMT + 0.5 mL of 10 M H2S04 + 0.5 mL of 0.05 M NaV03 + 2 mL of 10M acetic acid+ 2 rnL of ferriin reagent+ 2 mL of I: I ammonia, diluted to 10 mL. 2. Blank.

MethodD One of the sens1ttve spectrophotometric methods

reported for vanadium(IV) involves reduction of ferriin by vanadium(IV) and subsequent measurement of the resulting ferroin 11

. In method D for PMT, an excessive amount of metavanadate was employed to oxidise the drug in H2S04 medium to colourless sulphoxide, and the resulting vanadium(IV) was made to reduce ferriin to orange-red ferroin in H2S04-CH3COOH medium which was measured at 510 nm after suitable adjustment of pH by adding ammonia. The absorbance of ferroin measured was found to be linearly dependent on the concentration of the drug which served as the basis of assay.

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0.7 .-------------------,

0.6

0.5

" : 0.4

-e 0

~ 0.3

0.2

0.1

0~-~--~--r--~--r--~-~ 0 0.5 1.5 2.5 3.5

Volume of PMT, mL

Fig. 6----Calibration curve for method D (0.4 to 2.5 mL of 250 J..lg mL- 1 of PMT+0.5 mL of 0.05 M NaV03 + 0.5 mL of 10M H2S04 + 2 mL of 10M acetic acid+ 2 mL of ferriin reagent+ 2 mL of I : I ammonia).

PMT, when added in increasing concentrations consumes metavanadate, and consequently there will be a concomitant increase in the concentration of vanadium(IV), the reduced form of metavanadate. This is observed as a proportional increase in the absorbance of ferroin colour on increasing the concentration of PMT (Fig. 5) . The increasing values of absorbance at 510 nm were plotted against increasing concentration of PMT to obtain a standard curve (Fig. 6). The reaction,

Fe(Phen)33+ +Y(IV) ~ Fe(Phenh 2

+

+Y(V)

is found to be favoured in the presence of H2S04 and CH3COOH 11

• Hence, 0.5 mL of 10 M H2S04 and 2 mL of 10 M CH3COOH in the presence of 2 mL of ferriin reagent were used to force the reaction to go to completion. Since the experimental conditions for determination of vanadium(IY) using ferriin reagent are well-established 11

, the conditions for the oxidation of PMT by metavanadate prior to the determination of vanadium(IV) were optimized. Since the oxidation of the drug was found to be slow in HCl or H3P04 medium, H2S04 was the medium of choice since the same medium was required for the colour formation step. A 0.5 mL of 10M H2S04 in a total volume of 4 mL was adequate to effect the oxidation of the drug in about 5 min.

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Indian J. Chern. Technol. , July 2003

Table I -Stoichiometry of reactants

Method Mass of PMT, mg n*

1.00 2.1 9

A 5.00 2.03

15.00 2.14 20.00 1.95

5.00 2.05 7.00 2.09

B 10.00 1.97 12.00 1.90

*n=No. of moles of metavanadate reacting with each mole of PMT Average vajue of three determinations

Since ferroin is reported 12 to possess sensitivity and stability in the pH range 2-9, the pH of the acidic solution was raised by adding 2 mL of 1:1 ammonia sol ution which was found sufficient. Larger volumes of ammonia are undesirable since iron(III) gets precipitated at high pH values.

Optical characteristics of spectrophotometric methods

Optical characteristics such as Beer's law limits, detection and quantification limits, molar absorptivity and Sandell sensitivity values are given in Table 1. Slope, intercept and correlation coefficient data obtained from the linear least squares treatment are also presented in Table 2. Linear dependence of absorbance on concentration ranges given in Table 2 is evident from the regression coefficient values of -0.9907 and 0.9774 for methods C and D respectively. It is apparent from the molar absorptivity values that method Dis more sensitive than method C.

Accuracy, precision and ruggedness of the proposed methods

The accuracy of the methods was ascertained by determining known amounts/concentrations of pure drug in three levels (within the working ranges) by the proposed methods . The precision \Y.as established by performing seven replicate determinations _ on the same solution containing PMT in different levels. The range, percent error, standard deviation and range of error are compiled in Tables 3 and 4, and reveal the high accuracy and precision of the methods.

The ruggedness of the methods was tested by determining of the precision on a day-to-day basis.

Basavaiah & Charan: Titrimetric and spectrophotometric methods for the determination of promethazine theoclate Articles

Analyses were performed on the same amounts/ concentrations (used to evaluate the within- day repeatability) each day for 5 days. Analysis of

Table 2---0ptical characteristics of the spectrophotometric methods

Characteristic Method C Method D

Reaction time, min. 20 5

Beer's Law limits, Jlg mL-1 0.0-125.0 10.0-60.0

Limit of detection, Jlg mL-1 2.60 0.39

Limit of quantification, Jlg 8.69 1.29 mL-1

Molar absorptivity, L mor1 2.64xl03 5.33 X 103

cm·1

Sandell sensitivity, (Jlg cm·2 0.189 0.093 per 0.001 A unit) Regression equation * Intercept, a 0.3684 0.0550

Slope, b - 0.0023 0.0085

Confidence interval of 0.3684 ± 0.0550 ± intercept, a 0.0571 0.1051 Confidence interval of -0.0023 ± 0.0085 ± s lope,~ 0.0006 0.0027 Correlation coefficient, r -0.9907 0.9774

* Y = a+bX where Y is the absorbance of concentration X in mL-1

variance applied to· the results showed that between day variability, as expected, was greater than within day variability. In terms of relative standard deviations, the within day values were less than 1.5% and between day values were under 2.0%. Th'e latter figure probably represents the best appraisal of the precision in daily routine use.

Application to dosage form The method was applied to the determination of

PMT in avornine tablets. The results given in Table 4 reveal the high accuracy and precision of the procedures. The results also compare well with those obtained by the BP method 13

• The calculated student's t-values are less than 2.77 at 95% confidence level whereas the F-values are below 6.39 indicating comparable accuracy and precision with the reference method 13

.

Recovery experiments were carried out by adding known amounts of pure PMT to previously analysed tablet extract and determining the total amount by the proposed methods. The percent recovery values of the pure drug added shown in Table 6 demonstrate that excipients such as talc, starch, alginate, stearate, lactose and gum acacia do not interfere in the methods.

Table 3--Accuracy and precision of titrimetric methods

Method A Amount Amount Range, Error, SD, RSD, % taken, found , mg mg % mg (n=5)

mg

5.00 4.93 1.10 1.40 0.11 2.33

10.0 9.79 0.35 2.10 0.13 1.32

15.0 15.09 0.46 0.60 0.23 1.52 '¥ At 95% confidence level.

Range of error, '¥ %

2.14

1.27

1.46

SD = Standard Deviation, RSD = Relative Standard Deviation

Amount Amount taken, mg found, mg

6.00 5.91

9.00 9.12

12.00 12.20

Method B Range, Error,

mg %

0.50 1.50

0.51 1.33

0.43 1.66

SD, RSD, % Range of mg (n=5) error,'¥ %

0.22 3.72 3.59

0.19 2.08 2.00

0.12 0.98 0.94

Table 4--Accuracy and precision of spectrophotometric methods

Method C Method D Drug Drug Range, Error, SD, Jlg RSD,% Range of Drug Drug Range, Error, SD, Jlg RSD, % Range of

taken, Jlg found, Jlg 11g mL-1 % mL-1 (n=5) error, '¥ % taken, 11g found , !lg Jlg mL· % mL-1 (n=5) error, '¥ % mL -1 mL-1 mL-1 mL-1 I

25.0 24.34 1.95 2.64 0.87 3.56 8.43 20.0 19.46 0.34 2.70 0.13 0.69 0.66

75 .0 74.39 1.17 0.81 0.57 0.77 0.73 40.0 40.91 2.35 2.27 0.89 2.16 2.26

100.0 101.27 2.22 1.27 0.89 0.88 0.85 60.0 60.20 0.94 0.33 0.38 0.63 0.61

'¥ At 95% confidence level. SD = Standard Deviation, RSD = Relative Standard Deviation.

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Table 5--Results of analysis of avomine tabletsljf (25 mg per tablet) by the proposed methods.

Method Found,• SD,mg RSD, % Student's t- value F-value mg (2.77) * (6.39)*

A 25.22 0.27 2.22 0.85 2.56 B 25 .28 0. 19 1.84 0.74 3.62 c 24.45 0.74 1.51 1.28 1.28 D 25.58 0.64 1.55 1.35 2.74

• Average value of five measurements. * Figures in the parenthesis are values at 95% confidence level.

ljf Marketed by Rhone-Poulenc.

Table ~esults of recovery study by the standard-addition method

Method Amount of PMT in tablet Amount of pure PMT Total found, mg or Recovery of pure extract, mg or ~tg ljl added, mg or ~g ljl ~g ljl PMT added, %*

5.0 5.0 9.74 97.40 A 5.0 10.0 15.14 100.90

5.0 15 .0 20.01 100.09 10.0 7.0 17.09 100.57

B 10.0 10.0 19.74 98.70 10.0 12.0 22.56 102.58

250.0 250.0 507.40 I 01.48 c 250.0 500.0 738.60 98.48

250.0 750.0 995.00 99.50 200.0 200.0 392.40 98.10

D 200.0 300.0 488.00 97.60 200.0 400.0 612.72 102.12

*Average of three determinations. ljl mg in methods A and B, f.lg in methods C and D.

Conclusions

The developed methods are rapid, accurate, precise and simple. They have the advantage of being applicable over wide ranges. The species employed for spectrophotometric methods are stable for months, thus permitting quantitative analysis to be carried out with good reproducibility as indicated by low values of RSD. The procedures do not involve heating or extraction step, and are not critically dependent on any experimental variable, and can be conveniently used for the routine determination of PMT in bulk sample and in tablets.

Acknowledgement

Thanks are due to M/s Rhone-Poulenc Ltd., India for gift sample of PMT.

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