ЖУРНАЛ АНАЛИТИЧЕСКОЙ ХИМИИ, 2009, том 64, № 8, с. 869-874
ОРИГИНАЛЬНЫЕ СТАТЬИ
YflK 543
SEQUENTIAL INJECTION TECHNIQUE FOR DETERMINATION OF PHENOXYBENZAMINE HYDROCHLORIDE AND METOCLOPRAMIDE
IN PHARMACEUTICAL FORMULATIONS
© 2009 Zhijun Guo*, Suling Feng**, Jing Fan**
*College of Life Science, Henan Normal University Xinxiang, 453007, China **College of Chemical an Environmental Sciences, Henan Normal University Xinxiang, 453007, China Received 11.02.2008; in final form 28.01.2009
A sequential injection analysis (SIA) system is described for the determination of phenoxybenzamine hydrochloride and metoclopramide using spectrophotometer as detector. The method is based on the detection of an unstable red intermediate compound resulting from the reaction of phenoxybenzamine hydrochloride or metoclopramide with the di-azotizating product of p-phenylenediamine with sodium nitrite in hydrochloric acid medium. The sampling frequency is 69 h-1 and 75 h-1 for phenoxybenzamine hydrochloride and metoclopramide, respectively. The linear range is 10-400 |g/mL for phenoxybenzamine hydrochloride with a detection limit of 0.081 |g/mL and 20-250 |/mL for metoclopramide with a detection limit of0.034 |g/mL. The RSD is 1.01 and 0.45% for phenoxybenzamine hydrochloride and metoclopramide, respectively. The proposed methods were used to determine phenoxybenzamine hydrochloride and metoclopramide in pharmaceuticals. The results are compared with those obtained by pharmacopoeia method.
Phenoxybenzamine Hydrochloride (POBH) is chemically named as N-(2-Chloroethyl)-N-(l-methyl-2-phenox-yethyl) benzylamine (Fig. 1). It is a long-acting, adrenergic, alpha-receptor-blocking agent, which can produce and maintain "chemical sympathectomy" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. At present, there is an analytical method based on single dot calibration [1]. However, its results significantly differ from those obtained by standard curve method. The other method is first derivative ultraviolet spectrophotometry [2], which is much longer and less automated.
Metoclopramide (MCP, 4-Amino-5-chloro-N-(2-(di-ethylamino)ethyl)-2-methoxybenzamide) (Fig. 2) is an effective medicine for treatment of migraine headache and may be effective when combined with other medicines [3]. It can increase the motility (movements and contractions) of the stomach and upper intestine. MCP is also used as an anti-emetic in the treatment of some forms of nausea and vomiting and to increase gastrointestinal motility [4]. Many analytical methods have been developed for the determination of metoclopramide, and most of them are based on fluorimetric [5], spectrophotometric [6,7], chromatographic [8,9] and flow injection techniques [10]. The fluorimetric method has a higher sensitivity, but solvent extraction is needed and the procedure is labor-consuming. The spectrophotometric method is chiefly based on the di-azotization reaction and is time-consuming. The chromato-graphic method needs long time for extraction and expensive instrumentation, so it is difficult to popularize. Compared with flow injection (FI) method, SIA mentioned in
this paper can save more samples and reagents, greatly decreasing the accumulation of toxic residues. More importantly, SIA is able to integrate and miniaturize the determination, and make it convenient and precise and implement automatic control. Recently, Jing Fan and Aijun Wang developed a SIA methodology for the rapid and sensitive determination of metoclopramide hydrochloride [11].
The technique of SIA was described by Ruzicka and Marshall for the first time in 1990 as an efficient tool for automated liquid handling [12]. Automation, rapidity of the analysis and low consumption of sample and reagents
CH3
, HCl
Fig. 1. Molecular Structure of Phenoxybenzamine Hydrochloride.
Cl
H2N
OCH3
Fig. 2. Molecular Structure of Metoclopramide.
870
GUO и др.
C
R2 S1 R
t
W
Fig. 3. Schematic diagram of sequential injection system for the determination of phenoxybenzamine hydrochloride and metoclo-pramide; C, carrier (H2O); SP, syringe pump; MPV, multi-position valve; HC, holding coil (200 cm x 0.5 mm i.d.); RC, reaction
coil (100 cm x 0.5 mm i.d.); R0, reagent blank (2.5 x 10-3 M HCl); R1, NaNO2 (0.10 M); R2, p-phenylenediamine (1.1 x 10-2 1
R3, p-phenylenediamine (1.8 x l0 2 M); 51, phenoxybenzamine hydrochloride in 2.5 x 10 2.5 x 10-3 M of HC1; D, detector; W, waste.
1-3
' M);
M of HCl; S2, metoclopramide in
are the most important features that favour the SIA technique for application in many fields of analysis, primarily for monitoring long term processes. SIA was used for dissolution tests of various pharmaceutical formulations, e.g. ibuprofen tablets [13], analgetic tablets with aspirin, phen-acetin and caffeine [14], and tablets with ergotamine tartrate [15]. In this paper, it has been found that p-phe-nylenediamine can be diazotized with sodium nitrite in hydrochloric acid medium and the diazotization product could react quickly with phenoxybenzamine hydrochlo-ride or metoclopramide in hydrochloric acid medium, producing an unstable red intermediate compound. Based on this, a simple SIA spectrophotometric method was proposed for the determination of phenoxybenzamine hydro-chloride and metoclopramide.
NH2
NH2
N=H I + N 1 =H
NaNO2—HC-*- Ф + i :
1 NH2 T N =H
2+
EXPERIMENTAL
Apparatus. A FIAlab 3500 sequential injection instrument (FIAlab Instruments Inc., USA) was used in all experiments in the mode shown in Fig. 3. Sample and reagent solutions were driven to the holding coil by the syringe pump (2500 |L) and eight-port rotary selection valve controlled by a computer (FIAlab for Windows 5.0 Revision E). Then, the solutions were propelled reversely to a detector through the reaction coil. The holding coil was made of 200 cm x 0.5 mm i.d. Teflon (PTFE) tubing. The reaction coils were PTFE tubing of 100 cm x 0.5 mm i.d. for determination of phenoxybenzamine hydrochloride and metoclopramide. All other tubing connections were made of 0.7 mm i.d. PTFE tubing. An USB2000-UV-vis spectrophotometer (Ocean Optics Inc., USA) was used as a detector with a Z-type flow cell with a 1 cm light path-length and connected with optical fibers.
Reagents and chemicals. Stock solutions (1.0 mg/mL) of phenoxybenzamine hydrochloride and metoclopramide (China Pharmaceutical and Biological Inspection Institute) were prepared by dissolving phenox-ybenzamine hydrochloride and metoclopramide in water.
Table 1. Sequence of operation of the sequential injection system
Sequence No. MPV position SP position Flow rate, (|L/s) Volume, (|L)a Function
POBH MCP POBH MCP
1 Left 100 100 910 965 Aspiration of carrier
2 8 Right 25 25 -400 -400 Cleaning of the detector
3 3(5) Right 50 60 100 60 Aspiration of sodium nitrite or p-phenylenediamine
4 2(4, 6) Right 60 50 120 55 Aspiration of sample or blank
5 7(3) Right 70 60 70 120 Aspiration of p-phenylenediamine or sodium nitrite
6 8 Right 90 100 -800 -800 Pushing into the flow cell and detection, waste
a "+" for aspirating in holding coil; "-" for pushing out holding coil.
(a)
A 0.8
20 40
t(s)
60
A 0.8
(b)
n 7'
20
40
60
t(s)
Fig. 4. Curves of absorbance time, a: POBH determination; b: MCP determination; 1, NaNO2 + HCL+ POBH + p-phenylenedi-amine; 2, NaNO2 + p-phenylenediamine + HC1; 3, p-phenylenediamine + POBH + HC1; 4, NaNO2 + POBH + HCl; 1\NaNO2 + + HCL + MCP + p-phenylenediamine; 2', NaNO2 + p-phenylenediamine + HCl; 3\ p-phenylenediamine + MCP + HCl; 4\ NaNO2 + MCP + HCl.
Working solutions were prepared by suitable dilution. Reagent solutions of 0.10 M NaNO? and 0.05 M HCl were prepared in water. Reagent solution (0.10 M) of p-phe-nylenediamine was prepared by dissolving 0.5407 g of p-phenylenediamine in 50 mL of 0.20 M HCl. The blank solution was 2.5 x 10-3 M HCl. The sample or standard solution represented the mixture of HCl and phenoxybenzamine hydrochloride or metoclopramide solution, in which the concentration of HCl was 2.5 x 10-3 M. All reagents were of analytical reagent grade. Water used in the experiment was deionized.
Procedure. The sequential injection manifold is illustrated in Fig. 3. Table 1 shows the sequence of operation of the sequence injection system. The absorbance A of the solution was determined at 482 nm for phenoxybenzamine hydrochloride and at 490 nm for metoclopramide. After determination of the absorbance A0 of the blank, the values of AA = A - A0 were calculated.
trite can couple with phenoxybenzamine hydrochloride (or metoclopramide) in hydrochloric acid medium. The maximum wavelength is 482 nm for phenoxybenzamine hydrochloride and 490 nm for metoclopramide. Furthermore, there is a linear relationship between AA and the concentration of phenoxybenzamine hydrochloride or metoclopramide.
Optimization of the conditions. In order to achieve maximum sensitivity of the system, the one-factor-at-time method was used to optimize experimental parameters. The concentration was 270 ^g/mL for phenoxybenzamine hydrochloride and 200 ^g/mL for metoclopramide.
Physical parameters. The sensitivity of the determination was strongly influenced by the order of sequential aspiration of samples and reagents. Different sequential aspirations induce different zones of thorough mixing of reactants. It was shown that the reaction zone was maximum and the sensitivity of determination was the highest
0
0
RESULTS AND DISCUSSION
The absorbance time curves corresponding to the system are shown in Fig. 4. Sodium nitrite and phenoxybenzamine hydrochloride (or metoclopramide) could not react in hydrochloric acid medium resulting in faint absorbance (Fig. 4, curves 4, 4'). Similar phenomena for p-phenylenediamine with phenoxybenzamine hydrochlo-ride (or metoclopramide) were also found (Fig. 4, curves 3, 3'). When p-phenyle
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