British Pharmacopoeia Method Research Articles

Nitroso-R-salt as a sensitive spectrophotometric reagent for the determination of paracetamol in pharmaceutical preparations

Nitroso-R-salt is proposed as a sensitive spectrophotometric reagent for the determination of paracetamol in aqueous solution. The method is based on the reaction of paracetamol with iron(III) and subsequent reaction with nitroso-R-salt to yield a green colored complex with maximum absorption at 720 nm. Optimization of the experimental conditions was described. The calibration graph was linear in the concentration range of 0.1 – 2.0 ?g mL-1 paracetamol with a molar absorptivity of 6.9 × 104 L mol-1 cm-1. The method was successfully applied to the determination of paracetamol in pharmaceutical preparations without any interference from common excipients. The method has been statistically evaluated with British Pharmacopoeia method and no statistical difference between methods was found at the 95% confidence level.

Invitro evaluation of the neutralising capacity of twenty brands of antacids in Lagos, Nigeria

The use of substandard drugs is a great threat to the lives of people in the community. Identification of substandard drugs is important to exclude their use in clinical practice. These drugs may lead to reduced efficacy of pharmacotherapy. Antacid preparations are weakly basic and consist of metal salts, most commonly aluminium hydroxide or magnesium hydroxide. These salts dissociate to neutralise gastric acid and form neutral salts. The ultimate goal of antacid therapy is to reduce the concentration and the total load of acid in gastric juice with a pH of 1.3 to a pH between 3.5 and 5.0. The aim of this work is to carry out an in-vitro test on the acid neutralising capacity (ANC) of commonly available antacid brands in Lagos market. The British pharmacopoeia (BP) method of analysis of antacids was adopted. Twenty different brands of antacid suspensions and tablets were analysed. Brand SH suspension gave the highest neutralising capacity, 101.65 ml +/- 0.15, while brand SN gave the lowest, 99.75 ml +/- 0.75. All the fourteen antacid suspensions analysed complied with the official specification and therefore passed the analysis. Brand TB tablet gave the highest acid neutralising capacity (ANC), 54.10 ml +/- 0.2 while brand TD 49.50 ml +/- 0.1 gave the lowest. All the six antacid tablet brands analysed passed the assay. The ANC of an antacid is a parameter used to measure the effectiveness of an antacid in relieving ulcer pain. The acid-neutralising capacity of the antacid brands analysed were within the BP specification. The acid neutralising capacity of antacids should be determined before administration.

DETERMINATION OF MICRO AMOUNT OF PARACETAMOL IN PHARMACEUTICAL PREPARATIONS BY MOLECULAR SPECTROPHOTOMETRIC METHOD

A simple and sensitive spectrophotometric method has been established for the determination of paracetamol. The method is based on the reaction of paracetamol with iron(III) sulfate. The produced iron(II) reacts with potassium hexacyanoferrate (III) forming Prussian blue colored product with a maximum absorption at 710 nm. Linearity was in the range 0.1 – 7.0 µg mL -1 paracetamol [2.5 – 175.0 µg / 25 mL] with a limit of detection (signal : noise = 3) of 0.038 µg mL 1 , a molar absorptive of 3.477 × 10 4 L mol -1 cm -1 , a Sandell sensitivity of 4.348 ng cm -2 , a relative error of less than ± 1.5% and a relative standard deviation of 0.745 – 1.002% depending on the paracetamol concentration. The proposed method was statistically applied to the determination of paracetamol in pharmaceutical preparations. The proposed method has been statistically evaluated with British Pharmacopeia method and no statistical difference between methods was found at the 95% confidence level.

The Quality of Different Diclofenac Sodium Tablet Formulations Sold in Pharmacies in Tanzania

Objective: The objective of this study was to investigate the possible reasons for decreased anti- inflammatory and analgesic activities in patients using generic diclofenac sodium tablet formulations (50mg) in Dar es Salaam. Methodology: Different diclofenac sodium tablet products from different manufacturers were collected from twelve wholesale pharmacies with good storage conditions. In total 80 samples were collected, with a minimum of five samples from each wholesale pharmacy. In addition a survey on brands available and the pricing of different diclofenac formulations in 120 retail pharmacies was conducted. Analyses of the sampled tablet formulations were performed at the laboratory of Tanzania Food and Drug Athority. Both validated British and United States Pharmacopoeia methods were used to perform the analyses. Results: On visual appearance of tablets, 18% of the collected samples had cracks and white patches on the coat. Same number of samples could not meet the requirements for drug content and disintegration rates respectively, whereas, 27 % failed the dissolution rate tests. Voltaren® (Norvatis Pharma, Switzerland), the originator's product was the most expensive, less available and a less bought product. Vivian® (Lincoln Pharma, India) and Dyclomax® (Medreich Laboratories, India) were sold cheapest and were available in all pharmacies including those in the peripheral part of the city. Conclusion: Low anti- inflammatory and analgesic response reported by many patients with different pain conditions could be associated with the use of poor quality diclofenac sodium. Tanzania Medical Journal Vol. 23 (2) 2008: pp. 20-23

Determination of atenolol in pharmaceutical formulations by diffuse reflectance spectroscopy

A simple analytical method for quantification of atenolol in pharmaceutical formulations by diffuse reflectance spectroscopy is described. The method is based on the reaction, on the filter paper surface, between the drug and p-chloranil producing a colored compound. The best reaction conditions were obtained with 20 µL of atenolol solution and 20 µL of p-chloranil. All reflectance measurements were carried out at 550 nm and the linear range was from 1.13x10-2 to 7.88x10-2 mol L-1 (r = 0.9992). The limit of detection was 2.80 x 10-3 mol L-1. The proposed method was successfully applied to analysis of different commercial brands of pharmaceutical formulations and the results obtained by the proposed method were in good agreement with those obtained using the British Pharmacopoeia method.

An improved method for the determination of Fc function of immunoglobulins

The Fc function assay of immunoglobulin G is performed to ensure that the biological activity of the molecule is not compromised during purification and storage. The current British Pharmacopoeia (BP) method is cumbersome, time consuming and requires a continuous source of fresh red blood cells. We have modified the technique to improve the convenience, throughput and reproducibility of the assay by using frozen red blood cells, a microtitre plate format and electronic derivative analysis for processing results. Immunoglobulin G samples were assayed using either the BP Fc function procedure or a new procedure incorporating frozen cells, microtitre format and electronic derivative analysis. The Fc function results demonstrated that there was no significant difference between the BP and the new improved procedure. In this study, we demonstrated that a new Fc function assay incorporating frozen red blood cells, microtitre format and derivative analysis of haemolysis curves has been shown to be comparable to the standard BP procedure. It offers a more convenient and quicker means of performing analysis of Fc function of immunoglobulins.

Simultaneous Determination of Phenylephrine Hydrochloride, Guaifenesin, and Chlorpheniramine Maleate in Cough Syrup by Gradient Liquid Chromatography

A simple and reliable high-performance liquid chromatographic method was developed for the simultaneous determination of mixture of phenylephrine hydrochloride (PHENYL), guaifenesin (GUAIF), and chlorpheniramine maleate (CHLO) either in pure form or in the presence of methylparaben and propylparaben in a commercial cough syrup dosage form. Separation was achieved on a C8 column using 0.005 M heptane sulfonic acid sodium salt (pH 3.4 +/- 0.1) and acetonitrile as a mobile phase by gradient elution at different flow rates, and detection was done spectrophotometrically at 210 nm. A linear relationship in the range of 30-180, 120-1800, and 10-60 microg/mL was obtained for PHENYL, GUAIF, and CHLO, respectively. The results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2002) method and showed that the proposed method is precise, accurate, and can be easily applied for the determination of the drugs under investigation in pure form and in cough syrup formulations.

Potentiometric Carbon Paste Electrodes for the Determination of Bismuth in Some Pharmaceutical Preparations

Abstract The construction and general performance characteristics of two novel potentiometric membrane sensors responsive to bismuth are described. The sensors are based on the use of ion-association complexes of tetraiodobismate(III) (TIB) anion with polyoxyethylene(10) octyl phenyl ether (1) and tris(1,10-phenanthroline)iron(II) (2) as exchange sites in a carbon paste matrix. The sensors show fast, stable, and near-Nernstian response for the mono-charged anion of tetraiodobismate(III) over the concentration range 1×10−3–1×10−6 mol dm−3 at 25 °C over the pH range 4.0–9.0 and 3.0–8.0 with an anionic slope of 51.5±0.5 and 53.0±0.4 per concentration decade for tetraiodobismate(III)-1 and -2 (sensor-1 and sensor-2), respectively. The lower detection limit was 4×10−6 and 2×10−6 mol dm−3 with a response time of 20–40 s for sensor-1 and sensor-2 in the same order. The selectivity coefficients for bismuth relative to a number of interfering anions and iodide complexes of some metal ions were investigated. Direct potentiometric determination of 1–200 μg cm−3 of bismuth in aqueous solution showed an average recovery of 98.4% and a mean relative standard deviation of 1.5% at 80.0 μg cm−3. The determination of bismuth(III) in suppositories and ointment dosage form in the present study was comparable with the British pharmacopoeia method.

PVC Membrane Sensor for Potentiometric Determination of Atropine in Some Pharmaceutical Formulations

The construction and general performance of a novel potentiometric membrane sensor for determination of atropine has been developed. It is based on the formation of the ion association complex of the atropinium cation with phosphotungstate counter anion as electroactive material dispersed in a PVC matrix, β‐Cyclodextrin and o‐nitrophenyl octyl ether serve as a plasticizer. The sensor shows a fast, stable, near Nernstian response for 1×10−2 M to 1×10−6 M atropine at 25°C over the pH range of 3–8 with a cationic slope of 51±0.5 mV/decade. The lower detection limit is 8×10−7 M and the response time is 20–45 sec. Selectivity coefficients of atropine, relative to a number of interfering substances, were investigated. There are negligible interferences caused by most of the studied cations, anions, and pharmaceutical excipients. The direct determination of atropine shows an average recovery of 98.6% and a mean relative standard deviation (RSD) of 1.6% at 100 µg/mL. The results obtained by determination of atropine in some formulations (atropine injection and eye drops) are favorably comparable with those obtained by the British Pharmacopoeia method. The developed membrane electrode has been used as end point indicator electrode for some potentiometric titrations.

PVC Membrane Sensors for Potentiometric Determination of Acebutolol.

The construction and general performance characteristics of two novelpotentiometric membrane sensors responsive to the acebutolol are described. Thesensors are based on the use of ion-association complexes of acebutolol (AC) withtetraphenylborate(TPB) (I) and phosphomolybdate(PM) (II) as exchange sites in a PVCmatrix. The sensors show a fast, stable and near- Nernstian for the mono charge cationof AC over the concentration range 1×10-3 - ~10-6 M at 25 °C over the pH range 2.0 -6.0 with cationic slope of 51.5 ± 0.5 and 53.0 ± 0.5 per concentration decade for AC-Iand AC-II sensors respectively. The lower detection limit is 6×10-6 M and 4×0-6 M withthe response time 20-30 s in the same order of both sensors. Selectivity coefficients ofAC related to a number of interfering cation and some organic compounds wereinvestigated. There are negligible interferences are caused by most of the investigatedspecies. The direct determination of 3 - 370 μg/ml of AC shows an average recovery of 99.4 and 99.5% and a mean relative standard deviation of 1 . 5 % at 100.0 μg/ml forsensor I and II respectively. The results obtained by determination of AC in tablets usingthe proposed sensors which comparable favorably with those obtained by the Britishpharmacopoeia method. In the present investigation the electrodes have been utilized asend point indicator for some precipitation titration reactions.

PVC Matrix Membrane Sensor for Potentiometric Determination of Triphenyltetrazolium Chloride and Ascorbic Acid

AbstractThe construction and performance characteristic of a potentiometric PVC membrane sensor for the determination of triphenyltetrazolium chloride (TPTCl) is described. The sensor is based on the use of triphenyltetrazolium (TPT)‐tetraphenylborate (TPB) ion pair as ion exchange sites in PVC matrix in presence of dioctylphathalte as plasticizer. The TPT membrane sensor shows a stable, near‐Nernestian response for 6×10‐6 ‐ 1×10‐2 M TPTCl at 25 °C over the pH range 3‐10 with cationic slope of 57.0 ± 0.5. The lower detection limit is 4×0‐6M and the response time is 10‐30 sec. Selectivity coefficients for TPTCl relative to a number of different cations and anions were investigated, which there is negligible interferences. However, iodide, bromide and thiocyanate were interfering. The determination of 2.0‐ 3340.0 μg/ml of TPTCl in aqueous solutions shows an average recovery of 98.5 % and a mean relative standard deviation of 1.9 at 160μg/ml. The proposed method has been used for indirect potentiometric determination of ascorbic acid in its pharmaceutical formulations which are comparable favorably with those of British pharmacopoeia method. Precipitation titrations involving TPTCl as titrant are monitored with NaTPB using the proposed membrane sensor; the inflection break is about 300 mV.

Papaverine PVC Membrane Ion‐Selective Electrodes Based on its Ion‐Exchangers with Tetraphenylborate and Tetrathiocyanate Anions

The construction and general performance of novel potentiometric membrane ion selective electrodes for determination of papaverine hydrochloride has been described. They are based on the formation of the ion association complexes of papaverine (PA) with tetraphenylborate (TPB)(I) or tetrathiocyanate (TTC)(II) counter anions as electro-active material dispersed in a PVC matrix. The electrodes show fast, stable, near Nernstian response for 1 x 10(-2) to 6 x 10(-5) M and 1 x 10(-2) to 1 x 10(-5) M for PA-TPB and PA-TTC respectively at 25 degrees C over the pH range of 3-5.0 with a cationic slope of approximately 56.5 +/- 0.5 mV/decade for both sensors respectively. The lower detection limit is 4 x 10(-5) and 8 x 10(-6) M for PA- I and PA-II respectively with fast response time ranging from 20-45 sec. Selectivity coefficients for PA relative to a number of interfering substances were investigated. There is a negligible interference from the studied cations, anions, and pharmaceutical excipients. The determination of 4.0- 3000.0 microg/ml of PA in aqueous solutions shows an average recovery of 99.1% and a mean relative standard deviation of 1.4 at 100microg/ml. The direct determination of PA in some formulations (Vasorin injection) gave results that compare favorably with those obtained using the British Pharmacopoeia method. Potentiometric titration of PA with sodium tetraphenylborate and potassium thiocyanate as titrants utilizing the papaverine electrode as an end point indicator electrode has been carried out.

Experimental Design Optimization of a Sequential Injection Method for Promazine Assay in Bulk and Pharmaceutical Formulations

Experimental design optimization approach was utilized to develop a sequential injection analysis (SIA) method for promazine assay in bulk and pharmaceutical formulations. The method was based on the oxidation of promazine by Ce(IV) in sulfuric acidic media resulting in a spectrophotometrically detectable species at 512 nm. A 33 full factorial design and response surface methods were applied to optimize experimental conditions potentially controlling the analysis. The optimum conditions obtained were 1.0 × 10−4 M sulphuric acid, 0.01 M Ce(IV), and 10 μL/s flow rate. Good analytical parameters were obtained including range of linearity 1–150 μg/mL, linearity with correlation coefficient 0.9997, accuracy with mean recovery 98.2%, repeatability with RSD 1.4% (n = 7 consequent injections), intermediate precision with RSD 2.1% (n = 5 runs over a week), limits of detection 0.34 μg/mL, limits of quantification 0.93 μg/mL, and sampling frequency 23 samples/h. The obtained results were realized by the British Pharmacopoeia method and comparable results were obtained. The provided SIA method enjoys the advantages of the technique with respect to rapidity, reagent/sample saving, and safety in solution handling and to the environment.

S-Benzylthiuronium PVC matrix membrane sensor for potentiometric determination of cationic surfactants in some pharmaceutical formulation

The construction and characteristic performance of s-benzylthiuronium ( s-BT)–PVC membrane sensor responsive for cetylpyridinium chloride (CPC) are described. The sensor is based on the use of s-BT–tetraphenylborate (TPB) ion pair as electroactive material in PVC matrix in presence of dioctylphthalate as solvent mediator. The membrane sensor shows a fast, stable and near Nernstian response for CPC over the concentration range of 6 × 10 −6–1 × 10 −3 M at 25 °C and pH range 6–12 with cationic slope of 57.0 ± 0.4. The lower detection limit is 4 × 0 −6 M and the response time is 10–30 s. Selectivity coefficients for CPC relative to a number of different species were investigated, which there is negligible intereferences are caused by most of investigated cations, anions, and some organic compounds. The determination of 2.0–350.0 μg/ml of CPC in aqueous solutions shows an average recovery of 98.8%and a mean relative standard deviation of 1.87% at 64.0 μg/ml. The determination of CPC in mouthwash pharmaceutical solution gave results that compare favorably with those obtained by the British pharmacopoeia method. The s-benzylthiuronium electrode has been utilized as an end point indicator electrode for some precipitation titration reactions involving CPC as titrant.

Chemometric optimization of a SIA promethazine hydrochloride assay method

A sequential injection analysis (SIA) method for the assay of promethazine hydrochloride, based on its oxidation by acidified cerium(IV), was optimized. Three chemometric approaches were applied: (i) factorial design (3 3 applied to surface plot and 2 3 applied to effect factor) for screening the potential interacting variables, (ii) univariant for optimizing insignificantly interacting variables and (iii) simplex for optimizing potentially interacting variables. The optimum experimental conditions were 30 μl of 0.38 mol/l sulphuric acid, 30 μl of 3.99 × 10 − 3 mol/l cerium(IV), 20 μl of promethazine hydrochloride and 20 μl/s flow rate. The detection limit was 7.032 × 10 − 5 mol/l and the calibration curve was linear up to 1.563 mol/l with a correlation coefficient 0.9998, accuracy range of 89.0–101.5%, relative standard deviation 1.1% ( n = 10) and sample frequency at least 20 samples/h. The method was applied to tablet form and validated with the British Pharmacopoeia method. The developed SIA method is fully automated, reproducible, sensitive, rapid and reagent-saving, and therefore suitable for routine control in tablets form.

Potentiometric Membrane Sensor for Determination of Saccharin

A potentiometric poly(vinyl chloride) membrane sensor for determination of saccharin is described. It is based on the use of Aliquat 336S-saccharinateion-pair as an electroactive material in plasticized PVC membranes with o-nitrophenyloctylether or dioctylphthalate. The sensor is conditioned for at least two days in 0.1 mol L−1 sodium saccharinate before use. It exhibits fast, stable and Nernstian response for saccharinate ions over the concentration range of 1.0 × 10−1–5.0 × 10−5 mol L−1 and pH range of 4.5–11. The sensor is used for determination of saccharin in some dosage forms. Results with an average recovery of 101% and a mean standard deviation of 0.2% are obtained which is compared favourably with data obtained using the British pharmacopoeia method. The sensor shows reasonable selectivity towards saccharin in presence of many anions and natural sweeteners.

Spectrophotometric determination of caffeine and theophylline in pure alkaloids and its application in pharmaceutical formulations

A novel-coupling reagent is used for the simple and sensitive spectrophotometric determination of caffeine (CF) and theophylline (TP) in pure or pharmaceutical formulations. The method is based on the oxidation of CF and TP with sodium metaperiodate in the presence of acetic acid, followed by coupling with 3-methyl 2-benzo thiazolinone hydrazone hydrochloride (MBTH), to produce a blue-colored product with a λ max of 630 nm. The method is reproducible and has been applied for the determination of CF and TP in the tablets. The results are comparable to those obtained with the British pharmacopoeia (BP) method. Common excipients used as additives in pharmaceutical preparations do not interfere in the proposed method.

Membrane Sensors for the Selective Determination of Thiopental

Novel miniaturized polyurethane (PU) membrane sensors in an all-solid state graphite support were developed, electrochemically evaluated and used for the assay of thiopental drug. The thiopental (T) sensors are based on the formation of ion-association complexes of thiopental with copper(II) and cobalt(II)-bathophenanthroline (bphen) counter anions as electroactive materials dispersed in a polyurethane matrix. The sensors show a linear response for thiopental over the range of 1 x 10(-1) - 5 x 10(-5) M thiopental at 25 degrees C over the pH range 6 - 11 with anionic slopes of -28.7 and -28.3 mV decade(-1) with Cu- and Co-bphen thiopental membrane sensors, respectively. These sensors exhibit a fast response time (25 - 45 s), a low detection limit (5 x 10(-6) M), a long lifetime (7 weeks) and good stability. The selectivity coefficients for thiopental sensors relative to the number of interfering anions, were investigated. These sensors were used for the direct potentiometry of thiopental in a pharmaceutical formulation and human serum. Results with mean accuracy of 99.8 +/- 0.5% of nominal were obtained, which compare well with data obtained using spectrophotometric (UV-Vis) and British Pharmacopoeia (BP) methods.

Two Spectrophotometric Assays for Dopamine Derivatives in Pharmaceutical Products and in Biological Samples of Schizophrenic Patients Using Copper Tetramine Complex and Triiodide Reagent

Two simple, rapid, and sensitive spectrophotometric methods are proposed for the determination of levodopa (LD). The first method is based on coupling of 4-aminoantipyrine (4-AAP) with one of the dopamine derivatives (LD, CD) to give a new ligand that reacts with copper tetramine complex to give intensely colored chelates. The colored products are quantified spectrophotometrically at 525 and 520 nm for LD and CD, respectively. The optimization of the experimental conditions is described. The method has been used for the determination of 19.7–69.0 and 18.1–54.3 μg mL−1 of LD and CD, respectively. The accuracy of the method is achieved by the values of recovery (100 ± 0.2%) and the precision is supported by the low standard deviation (SD = 0.17–0.59) and relative standard deviation (CV = 0.4%–1.54%) values. The second method is based on the formation of ion-pair iodinated inner sphere or outer sphere colored complexes between the LD and triiodide ions at pH 5 and room temperature (23 ± 3°C). This method has been used for the determination of LD within the concentration range 39.44–78.88 μg mL−1 with SD = 0.22–0.24 and recovery percent = 100 ± 0.3%. The sensitivity of the two methods is indicated by Sandell's sensitivity of 0.014–0.019 g cm−2. The results of the two methods are compared with those of the official method. The interference of common drug additives, degradation products, and excipients was also studied. The proposed methods were applied successfully to the determination of the LD-CD synthetic mixture and Levocare drug. The determination of LD in urine of some schizophrenic patients was applied with good precision and accuracy. The reliability of the methods was established by parallel determinations against the official British pharmacopoeia method.

LC and UV determination of flavonoids from Passiflora alata medicinal extracts and leaves

The leaves of Passiflora alata Curtis (an official species in the Brazilian Pharmacopoeia) are used to treat anxiety, as antispasmodics and sedatives. The development of new analytical methods for analysing flavonoids in Passiflora species is needed in order to improve the quality assurance of the plant and derived extracts and phytomedicines. A survey on the profile of flavonoids and content of isovitexin in the leaves and fluidextract of P. alata through LC was carried out, comparing its chromatographic profiles with a commercial P. incarnata fluidextract. Also, the concentration of the total flavonoids of extracts and leaves according to phamarcopoeial photometrical methods was determined and discussed. The fluidextract of P. alata was produced in accordance with the Pharmacopoeia Helvetica method; the presence of isovitexin in both species (which have distinct chromatographic profiles) was evidenced, this being the major flavonoid compound in the P. incarnata (1.198 g%), but not in P. alata (0.018 g%) fluidextract. Only traces of vitexin could be observed in the P. alata, as well as the absence of the other tested flavonoids: orientin and swertisin ( P. incarnata markers), hyperoside, rutin, hesperidin and clorogenic acid. The LC developed method was shown to be appropriated for the qualitative and quantitative analyses and for differentiate species, suitable to be applied to commercial sample analysis. The spectrophotometrical results of three different methods described for P. incarnata were not comparable, the best performance being the British Pharmacopoeia method.