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Boletín de la Sociedad Chilena de Química

versión impresa ISSN 0366-1644

Bol. Soc. Chil. Quím. v.47 n.2 Concepción jun. 2002

http://dx.doi.org/10.4067/S0366-16442002000200013 

Bol. Soc. Chil. Quím., 47, 163-168 (2002)

 

A PETHIDINE SELECTIVE POLYMERIC MEMBRANE ELECTRODE

Zhi Hua. Liu 1, Meng Liang Wen 1*, Yun Yao 1, Jie Xiong 2

1 Department of Chemistry, Yunnan University, Kunming, Yunnan 650091, PR China
2 Experimental Center, Yunnan University, Kunming, Yunnan 650091, PR China
Corresponding author: Prof. Meng-Liang Wen
Department of Chemistry, Yunnan University, Kunming, Yunnan 650091,PR China
Phone: +86 871 503 3571, Fax: +86 871 515 3832, E-mail: mlwen@ynu.edu.cn
(Received: February 23, 2000 - Acepted:March 18, 2002)

SUMMARY

A novel plastic poly (vinyl chloride) membrane electrode based on pethidine-reineckate ion-association complex as ion-exchange site for determination of pethidine hydrochloride in injections and tablets was described, in which the plasticizer was dibutyl phthalate. The linear response covered the range of 1x10-5~1x10-3 M drug concentration with a slope of 53.50 mV/decade. The practical pH range was 2~8. The lower detection limit was 4.36x10-6 M. There was negligible interference from a number of inorganic and organic cations and some common drug excipients. The proposed electrode had been successfully applied to determine pethidine hydrochloride in tablets and injections. The results were correlated well with those obtained by the United States Pharmacopoeia standard procedure.

KEY WORDS: pethidine hydrochloride, polymeric membrane electrode, potentiometry, pharmaceutical analysis

RESUMEN

Se describe un nuevo electrodo de membrana basado en poli (vinilcloruro) con el complejo de asociación iónica demerol-Reinikato como sitio de intercambio para la determinación de demerol clorhidrato, tanto en inyecciones como en tabletas, en el cual se usa ftalato de dibutilo como plastificante. La respuesta lineal cubre el rango de concentración 1%10-5i1%10-3 M con una pendiente de 53.50 mV/decada. El rango práctico de pH fue 2 i 8. El límite más bajo de detección fue de 4.36%10-6 M. Hubo una interferencia insignificante de un número de cationes inorgánicos y orgánicos y de algunos excipientes comunes de drogas. El electrodo propuesto ha sido aplicado exitosamente para determinar el clorhidrato de petidina en tabletas e inyecciones. Los resultados están bien correlacionados con aquellos obtenidos por el procedimiento estandar de la Farmacopea de estados Unidos.

PALABRAS CLAVES: demerol-reinikato, electrodo de membrana polimérica, potenciometría, análisis farmacéutico.

INTRODUCTION

Pethidine hydrochloride (Meperidine hydrochloride, Dolantin) is an important narcotic analgesic, which has been employed in the treatment of a variety of medical conditions for many years [1]. While being a potent analgesic, the pethidine hydrochloride is also an analogue of illicit drugs, such as heroine. Therefore, it is a controlled substance (opiate) on the list of regulations of many countries. To improve the knowledge of pharmacology of pethidine hydrochloride and control it effectively, many methods have been developed for its determination, such as HPLC [2, 3], GC [4, 5], GC/MS [6, 7], colourimetry [8] and spectrophotometry [9], etc., in which the samples have to be pretreated tediously.

Ion-selective membrane electrode (ISME) is useful in pharmaceutical analysis due to its low cost, ease of use and maintenance, and the simplicity and speed of the assay procedures [10-12]. To determine pethidine hydrochloride in pharmaceutical formulations, Z. Mitsana-Papazoglou et al. have developed a liquid membrane pethidine-selective electrode to determine pethidine in injection [13]. They used p-nitrocumene as solvent to dissolve ion association of pethidine with tetrakis(m-chlorophenyl) borate and prepared a liquid membrane electrode sensitized to pethidine. However, p-nitrocumene was a carcinogenic compound and could leak during measurements. Thus, it was not suitable for practical applications. In this paper we have developed a novel plasticized poly (vinyl chloride) (PVC) membrane electrode based on pethidine-reneickate ion-association complex as electroactive material for determination of pethidine hydrochloride in injections and tablets, in which dibutyl phthalate (DBP) used as a plasticizer. It had been successfully applied to determine pethidine hydrochloride in tablets and injections The results correlated well with those obtained by the United States Pharmacopoeia (USP) standard procedure [14]. Compared with previous pethidine liquid membrane electrode, the plasticized membrane electrode was more stable and had a longer life; in particular, its PVC-based membrane separated the inner solution and the sample effectively, thus it could be used continuously without significant change of response.

EXPERIMENTAL PART

Reagents and Apparatus
All solutions were prepared with dionized water (>1MW). The chemicals used were all of analytical grade. Reneickate and poly (vinyl chloride) (PVC, high molecular weigh) were obtained from Fluka. Dibutyl phthalate was obtained from Sigma. Monobasic potassium phosphate, triethylamine and acetonitrile were obtained from the local chemical suppliers. The pethidine hydrochloride reference standard was obtained from the National Anesthetic Drug Laboratory, Beijing, PR China. Its characteristic was consistent with the USP [14]. The standard was treated according to the USP before use [14]. The tablets and injections of pethidine hydrochloride were purchased from local drug store. 25mg/tablet, 50mg/tablet, and injection of 50mg/ml were manufactured by Qinghai Pharmaceutical Factory, Qinghai, PR China. Injection of 100mg/ml was produced by Yichang Pharmaceutical Factory of Hubei, Hubei, PR China.

Potentiometric measurements were made with a PHs-3C Digital pH-meter (Shanghai Rex Instrument Factory, Shanghai, PR China). The external reference electrode was a model 801 double-junction saturated calomel electrode with outer bridge electrolyte (Jiangsu Electroanalytical Instrument Factory, Jiangsu, PR China). A model E-201-C complex electrode (Shanghai Rex Instrument Factory, Shanghai, PR China) was used to measure the pH.

A XW-80A Vortex (Medicine University of Shanghai, Shanghai, PR China) and a CSF-1B ultrasonic generator (Shanghai Ultrasonic Instrument Factory, Shanghai, PR China) were used in treatment of the tablets.

ALC/GPC model 201 HPLC (Waters, USA) and DL-800 Chromatographic Working Station (Dalian Elite Scientific Instruments Co. Ltd., Liaoning, PR China) were employed for determination tablets and injections of pethidine hydrochloride by USP standard procedure.

Construction of the Electrode
The ion-association complex was prepared by mixing stoichiometric amounts of 10-2 M solution of reneickate with an equimolar solution of pethidine hydrochloride. The precipitate was filtered and washed with deionized water several times. Then the precipitate was dried under 25 C in vacuum for at least 48 h. The ion-association complex should be stored in a dryer to keep it free from dust and moisture in the air. The master membrane was prepared according to a procedure described by Craggs [15]. The PVC-membrane composition was 2.0 wt % pethidine-reneickate ion-association complex, 49.0 wt % dibutyl phthalate and 49.0 wt % PVC. The electrode body was filled with an inner filling solution containing 10-1 M NaCl and 10-3 M pethidine hydrochloride. The finished electrode was preconditioned overnight by soaking it in a 10-3 M pethidine hydrochloride solution (saturated with AgCl). The electrode must be washed with deionized water before measurement. It could be kept in air when used continuously. The inner filling solution should be removed when it is not used for an extended period of time. All potentiometric measurements were performed using the following cell assembly: Ag/AgCl(KCl (satd.)||salt bridge((sample solution|membrane|10-1 M NaCl + 10-3 M pethidine hydrochloride||Ag/AgCl

Direct Potentiometry
Standard solutions of 1x10-3 M~1x10-8 M were prepared by serial dilution of a 1x10-2 M pethidine chloride solution. The electrodes were placed into well stirred 10 ml of standard solutions in the range of 1x10-8 M~1x10-2 M and potentials were recorded. Calibration graph was obtained by plotting E (mV) vs. pC. With the mean potential of five measurements the unknown concentration could be derived from the regression equation of calibration graph.

Standard Addition Method
An electrode was immersed into a sample of 10 ml with unknown concentration (ca. 10-4 M) for 30 s and the equilibrium potential of E1 was recorded. Then 0.1 ml of 1x10-2 M of pethidine hydrochloride standard was added into the testing solution and the equilibrium potential of E2 was obtained after 30 s. From the change of DE (E2-E1) one can determine the concentration of the testing sample[16].

HPLC Measurement
The measurement was carried out under the condition that the column was (Bondapak C18, 3.9x300 mm. Equal volumes (about 20 ml) of the standard solution and testing sample were injected into the chromatograph separately, and the chromatograms were recorded. Then the responses were measured. From the measurement data the quantity of pethidine hydrochloride in the sample can be calculated [14].

RESULTS AND DISCUSSION

A typical calibration graph in Figure 1 shows that electrode response was linear in the range of 1x10-5 M~1x10-3 M pethidine hydrochloride solution. The critical characteristics of the electrode are summarized in Table 1. The stability of the electrode response was checked over a period of 3 months. The time required for the electrode to reach 95% of final response exhibited good stability. The electrode response displayed good stability and reproducibility over the test, as shown by the relative standard deviation values as in Table I.

The effect of pH on the electrode potential was investigated by observing the changes in the potential readings with pH of the solutions (1x10-5 M~1x10-3 M pethidine hydrochloride solution) after addition of small volumes of 3M HCl and/or 3M NaOH. It was found that the pethidine-sensitive membrane electrode based on pethidine-reneickate ion-association complex showed virtually no pH response over the range of 2-8 pH units in Figure 2. That means the protonation form of pethidine could be maintained in the range of 2-8 pH. In strong acidic media, break may be due to the protonation of the ion association complex within the membrane. In alkaline media, the measurements were hindered owing to the deprotonation of pethidine and formation of free pethidine precipitate in the test solutions.

Potentiometric selectivity coefficient defines the ability of an ion-selective electrode to distinguish a particular ion from others [16]. It is one of most important characteristic of an ion-selective electrode, as it often determines whether a reliable measurement in the target sample is possible. The interference of various ions and uncharged substances on selectivity of proposed electrode were studied by the separated solution method (SSM) recommended by IUPAC [16]. The potentiometric selectivity coefficients (KPot) were listed in Table II. There were no significant interference from most of the tested substances with the exception of berberine, fentanyl, thebaine, cinchoine, picric acid, and procaine. Fortunately, these interferences were absent in pethidine hydrochloride tablets or injections. The proposed electrode exhibited reasonable selectivity towards pethidine hydrochloride.

The proposed electrode was employed for the assay of pethidine content in injection and tablet by the standard addition method. The results of the potentiometric methods compared with the USP standard procedure were shown in Table III. As could be seen in Table 3, high precision was obtained (RSD<1%) by the potentiometric method.

According to the results above, one could conclude that the pethidine-selective plastic membrane electrode based on pethidine-reneickate ion-association complex in a PVC matrix exhibited useful analytical characteristics for the determination of pethidine hydrochloride in pharmaceutical preparations. Therefore, it could be useful for on site rapid analysis of pethidine hydrochloride during clinical monitoring and quality control of pharmaceutical production.

ACKNOWLEDGEMENTS

The authors gratefully acknowledged support from the Natural Science Fund of Yunnan and the Science Fund of Yunnan Education Committee.

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*Corresponding author: Phone: +86 871 503 3571, Fax: +86 871 515 3832, E-mail: mlwen@ynu.edu.cn