Study on the determination of metronidazole in human serum by adsorptive stripping voltammetry

In Britton-Robinson buffer, metronidazole is preconcentrated on a HMDE at 0.0 V (vs. AgAgCl). An adsorptive stripping peak is observed at -0.62 V. The response is linear from 1 x 10(-8) to 1 x 10(-6)M with 1.5 min accumulation. The method has been successfully applied to the determination of metronidazole in human serum and formulations.     

Preparation and evaluation of topical microemulsion system containing metronidazole for remission in rosacea

The aim of this study was to prepare a topical water-in-oil type microemulsion containing metronidazole and to compare its effectiveness with a commercial gel product in the treatment of rosacea. A pseudo-ternary phase diagram (K(m)=2:1) was constructed using lecithin/butanol/isopropyl myristate/water. The microemulsion was chosen from the microemulsion region in the phase diagram. The formulation was a water-in-oil type microemulsion (droplet size: 11.6 nm, viscosity: 457.3 mPa·s, conductivity: 1.5 μs/cm, turbidity: 6.89 NTU) and the addition of the metronidazole did not alter the properties of the system. The release experiment showed that the release rate of metronidazole from the commercial gel product was higher than that of the microemulsion. Stability experiments showed that the metronidazole microemulsion remained stable for at least 6 months; none of the characteristic properties of the microemulsion had changed, the system retained its clarity and there was no sign that crystallization of metronidazole has occurred. Microemulsion was compared to a gel product in a randomized, double-blind, baseline-controlled, split-face clinical trial for the treatment of patients. After the 6-week treatment period there was a statistically significant difference in reduction of the main symptoms of rosacea. Of the patients treated with the microemulsion, 17% experienced complete relief from inflammatory lesions, and 50% from erythema. The microemulsion resulted in complete relief in 38% of the patients with telangiectasia while the commercial product did not provide any relief of telangiectasia symptoms. In conclusion, the microemulsion containing metronidazole was found to be more effective in reducing the symptoms of rosacea compared to the commercial gel product.     

Thermosensitive mucoadhesive gel formulation loaded with 5-Fu: cyclodextrin complex for HPV-induced cervical cancer

Human Papilloma Virus (HPV) infections are the major cause of cervical cancers. To achieve a better therapeutic efficacy and patient compliance in the treatment for HPV-induced cervical cancers, anticancer agent 5-fluorouracil has been formulated in a vaginal gel using the thermosensitive polymer Pluronic^® F127 together with alternative mucoadhesive polymers e.g., hyaluronic acid, Carbopol 934 and hydroxypropylmethylcellulose. To increase its aqueous solubility and to achieve the complete release of 5-FU from the gel, the drug was incorporated as its inclusion complex with 1:1 molar ratio with either β-cyclodextrin or hydroxypropyl-β-cyclodextrin. Following the characterization of drug:CD complexes, thermosensitive gel formulations containing different mucoadhesive polymers and the drug in free or complexed form were characterized in vitro by determining the gelation temperature and the rheological behavior of different formulations along with the in vitro release profiles of these formulations in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin accelerated the release of 5-FU with the exception of formulation containing Carbopol 934 as mucoadhesive polymer. As far as rheological properties are concerned, favorable thermosensitive in situ gelling properties were obtained with formulations containing HPMC as mucoadhesive polymer. Complete release of 5-FU from gels were obtained with both complexes of β-CD and HP-β-CD and cytotoxicity studies against HeLa human cervical carcinoma cells demonstrated that 1% 5-FU:CD complexes were equally effective as 1% free 5-FU indicating better therapeutic efficacy with lower dose.     

Pharmacokinetics of metronidazole in rat blood,brain and bile studied by microdialysis coupled to microbore liquid chromatography

Metronidazole is a synthetic nitroimidazole-derived antibacterial and antiprotozoal agent used for the treatment of infections involving gram-negative anaerobes. The aim of this study is to develop an in vivo microdialysis with microbore high-performance liquid chromatographic system for the pharmacokinetic study of metronidazole in rat blood, brain and bile. In addition, to investigate the disposition mechanism of metronidazole, the P-glycoprotein modulator and cytochrome P450 inhibitor were concomitantly administered. Separation of metronidazole from various biological fluids was applied to a microbore reversed-phase ODS 5 microm (150 x 1 mm I.D.) column. Its mobile phase consists of an acetonitrile-50 mM monosodium phosphate buffer (pH 3.0) containing 0.1% triethylamine (10:90, v/v) with a flow-rate of 0.05 ml/min. The UV detector wavelength was set at 317 nm. The results suggest that metronidazole penetrates the blood-brain barrier (BBB) and goes through hepatobiliary excretion. However, these pathways of BBB penetration and hepatobiliary excretion of metronidazole may not be related to the P-glycoprotein.     

Controlled drug release from gels using lipophilic interactions of charged substances with surfactants and polymers

The aim of this article was to study interactions between different gel forming polymers and amphiphilic drugs and surfactants with the intention of finding interactions that can be used for designing controlled release formulations. The release from gels was measured by detecting the UV-absorbance of drugs released from 6 mL gel into 250 mL release medium in a dissolution bath. The rheological behavior of gels was characterized using a controlled rate rheometer. The diffusion coefficient of alprenolol was 6.3 x 10(-6) cm(2)/s when formulated in a 1% poly(acrylic acid) gel (PAA) and 2.8 x 10(-6) cm(2)/s in a lipophilically modified gel (LM-PAA). The addition of alprenolol to 1% LM-PAA increased the elasticity, G', from 123 to 182 Pa. Increased gel strength was also observed for a number of other amphiphilic drugs. The addition of 1% Brij 58 to LM-PAA decreased the diffusion coefficient of alprenolol to 2.3 x 10(-6) cm(2)/s. It was possible to sustain the release of charged drugs with high log P by adding surfactant micelles. However, the effect was small and only useful for drugs with adequate lipophilicity. The interaction between LM-PAA and amphiphilic drugs could be seen using rheology and was used for designing controlled release gel formulations. In this way surfactants can be avoided, thus decreasing toxicity problems.     

高效液相色谱法同时测定祛痘产品中6种抗生素及甲硝唑

建立了一种高效液相色谱-二极管阵列检测器(HPLC-DAD)同时测定祛痘产品中6种抗生素(盐酸美满霉素、土霉素、盐酸四环素、盐酸金霉素、盐酸多西环素和氯霉素)及甲硝唑的分析方法。样品用甲醇提取,采用Agilent ZORBAX SB-C18色谱柱(250 mm×4.6 mm, 5 μm)分离;以甲醇、乙腈和0.002 mol/L草酸为流动相进行梯度洗脱,流速0.8 mL/min;柱温20 ℃,检测波长268 nm,进样量10 μL,外标法定量。结果表明,6种抗生素及甲硝唑在1～30 mg/L范围内呈良好的线性关系,相关系数(r)均不低于0.9970;方法检出限为1.1～1.2 μg/g;高、中、低(5、10、20 mg/L) 3个添加水平下的回收率为91.9%～107.7%,相对标准偏差(RSD)为0.13%～1.74%。应用该方法对祛痘产品进行检验,15%的样品中检出甲硝唑。该方法具有灵敏、准确、快速、分离效果好的优点,适用于祛痘产品中6种抗生素及甲硝唑的检测。     

Capillary electrophoresis/electrochemical detection system with on-line deoxygenation

A capillary electrophoresis (CE)/electrochemical detection system with on-line deoxygenation was developed, consisting of a deoxygenation injector, a deoxygenation protector, and an electrochemical detection cell. When the system was utilized for 60 min, the steady-state current of oxygen detected could be dropped to 3% of the original value for the gold/mercury amalgam electrode and to 8% of the original value for the gold electrode, and the limit of detection could be decreased two orders of magnitude for the reducible analytes such as TI+ (from 3.1 x 10-5 mol/L to 8.0 x 10-7 mol/L) and metronidazole (from 3.8 x 10-5 mol/L to 4.0 x 10-7 mol/L).     

New solid mucoadhesive systems for benzydamine vaginal administration

The aim of this work was the realization of new formulations for vaginal application to improve the pharmacological effect of benzydamine, displaying both anti-inflammatory and antiseptic activities. For this reasons, this drug was formulated in solid dispersions, by using the mucoadhesive polymers HPMC and/or Carbopol(?), then compressed. Tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion and in vitro release. Kinetics, responsible for drug delivery, was investigated as well. Tablets prepared by using only HPMC showed the best results in terms of swelling and mucoadhesion (time and force) together with prolonged and complete drug release, by diffusive mechanism, through gelled layer. Despite the good mucoadhesive properties, Carbopol(?) does not represent a good excipient because, after the contact with water, it generates a spongy gel layer, not homogeneous, stiff, brittle and with breaking tendency when highly swelled. This kind of gel does not guarantee a linear drug release and could provoke discomfort because of fragment release. HPMC mucoadhesive tablets could be a proper delivery system for benzydamine administration representing a good alternative to traditional dosage forms for vaginal topical therapy.     

Application of DSC and NIRS to study the compatibility of metronidazole with different pharmaceutical excipients

The purpose of the present work was to study the compatibility of metronidazole with different pharmaceutical excipients (hydroxypropyl methylcellulose, poly(ethylene oxide), microcrystalline cellulose, dicalcium phosphate dihydrate, and anhydrous dicalcium phosphate) using differential scanning calorimetry and diffuse reflectance spectroscopy. Dicalcium phosphate dihydrate was the only excipient that showed interaction with metronidazole even before storage. Changes referring to a possible transition to dihydrate form were observed in the thermal curves of anhydrous dicalcium phosphate after four weeks of storage. Although dicalcium phosphate dihydrate can be replaced by the anhydrous form in pharmaceutical formulations, the observed transition might negatively influence the stability of dosage forms.     

Nanoemulsification Improves the Pharmaceutical Properties and Bioactivities of Niaouli Essential Oil (Melaleuca quinquenervia L.)

We develop a suitable delivery system for niaouli essential oil (NEO) using a nanoemulsification method for acne vulgaris. Prepared nanoemulsions (NEs) were characterized for droplet dimension, rheology, surface charge, and stability. The ability of NEO formulations against Propionibacterium acnes and Staphylococcus epidermidis was investigated and all formulations showed antiacne potential in vitro. Ex vivo permeation studies indicated significant improvement in drug permeations and steady state flux of all NEO-NEs compared to the neat NEO (p < 0.05). On the basis of the studied pharmaceutical parameters, enhanced ex vivo skin permeation, and marked effect on acne pathogens, formulation NEO-NE₄ was found to be the best (oil (NEO; 10% v/v); Kolliphor EL (9.25% v/v), Carbitol (27.75% v/v), and water (53% v/v)). Concisely, the in vitro and ex vivo results revealed that nanoemulsification improved the delivery as well as bioactivities of NEO significantly.     

Design and in vitro evaluation of zidovudine oral controlled release tablets prepared using hydroxypropyl methylcellulose

Oral controlled release matrix tablets of zidovudine were prepared using different proportions and different viscosity grades of hydroxypropyl methylcellulose. The effect of various formulation factors like polymer proportion, polymer viscosity and compression force on the in vitro release of drug were studied. In vitro release studies were carried out using United States Pharmacopeia (USP) type 1 apparatus (basket method) in 900 ml of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using Zero-order model equation, Higuchi's square-root equation and Ritger-Peppas' empirical equation. Compatibility of drug with various formulations excipients used was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 10% hydroxypropyl methylcellulose (HPMC) 4000 cps were found to show a good initial drug release of 21% in the first hour and extended the release upto 16 h. Matrix tablets containing 20% HPMC 4000 cps and 10% HPMC 15000 cps showed a first hour release of 18% and extended the release upto 20 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of zidovudine, with good initial release (17-25% in first hour) and which extend the release upto 16-20 h, can overcome the disadvantages of conventional tablets of zidovudine.     

Quantitative assay of metronidazole by capillary zone electrophoresis with amperometric detection at a gold microelectrode

Capillary zone electrophoresis was employed for the determination of metronidazole using end-column amperometric detection with a gold microelectrode at a constant potential of -0.52V vs. saturated calomel electrode. To overcome interference of oxygen in the solution, a deaeration injector and a deaeration protector at the detection cell were used. The optimum conditions of separation and detection are 1.0 x 10(-3) mol/L potassium dihydrogen citrate (KH2C6H5O7) for the buffer solution, 20 kV for the separation voltage, and 5 kV and 10 S for injection voltage and injection time, respectively. The limit of detection is 6.0 x 10(7) mol/L or 0.78 fmole (S/N = 3). The relative standard deviation is 3.9% for the electrophoretic peak current. The method was applied to the determination of metronidazole in human urine.     

In situ gelling hexagonal phases for sustained release of an anti-addiction drug

In this study, fluid precursor formulations for subcutaneous injection and in situ formation of hexagonal phase gels upon water absorption were developed as a strategy to sustain the release of naltrexone, a drug used for treatment of drug addiction. Precursor formulations were obtained by combining BRIJ 97 with propylene glycol (PG, 5-70%, w/w). To study the phase behavior of these formulations, water was added at 10-90% (w/w), and the resulting systems were characterized by polarized light microscopy. Two precursor formulations containing BRIJ:PG at 95:5 (w/w, referred to as BRIJ-95) and at 80:20 (w/w, referred to as BRIJ-80) were chosen. Naltrexone was dissolved at 1% or suspended at 5% (w/w). Precursor formulations were transformed into hexagonal phases when water content exceeded 20%. Water uptake followed second-order kinetics, and after 2-4h all precursor formulations were transformed into hexagonal phases. Drug release was prolonged by the precursor formulations (compared to a drug solution in PBS), and followed pseudo-first order kinetics regardless of naltrexone concentration. The release from BRIJ-80 was significantly higher than that from BRIJ-95 after 48 h. The relative safety of the precursor formulations was assessed in cultured fibroblasts. Even though BRIJ-95 was more cytotoxic than BRIJ-80, both precursor formulations were significantly less cytotoxic than sodium lauryl sulfate (considered moderate-to-severe irritant) at the same concentration (up to 50 μg/mL). These results suggest the potential of BRIJ-based precursor formulations for sustained naltrexone release.     

Hydrogen‐Bonded Complexes and Blends of Poly(acrylic acid) and Methylcellulose: Nanoparticles and Mucoadhesive Films for Ocular Delivery of Riboflavin

Poly(acrylic acid) (PAA) and methylcellulose (MC) are able to form hydrogen‐bonded interpolymer complexes (IPCs) in aqueous solutions. In this study, the complexation between PAA and MC is explored in dilute aqueous solutions under acidic conditions. The formation of stable nanoparticles is established, whose size and colloidal stability are greatly dependent on solution pH and polymers ratio in the mixture. Poly(acrylic acid) and methylcellulose are also used to prepare polymeric films by casting from aqueous solutions. It is established that uniform films can be prepared by casting from polymer mixture solutions at pH 3.4–4.5. At lower pHs (pH < 3.0) the films have inhomogeneous morphology resulting from strong interpolymer complexation and precipitation of polycomplexes, whereas at higher pHs (pH 8.3) the polymers form fully immiscible blends because of the lack of interpolymer hydrogen‐bonding. The PAA/MC films cast at pH 4 are shown to be non‐irritant to mucosal surfaces. These films provide a platform for ocular formulation of riboflavin, a drug used for corneal cross‐linking in the treatment of keratoconus. An in vitro release of riboflavin as well as an in vivo retention of the films on corneal surfaces can be controlled by adjusting PAA/MC ratio in the formulations.     

Spectrophotometric determination of acyclovir and ribavirin in their dosage forms

Two simple, accurate, and reliable spectrophotometric methods have been developed for the determination of 2 antiviral drugs, acyclovir (ACV) and ribavirin (RBV), in their pharmaceutical formulations. These methods are based on oxidation of the 2 drugs with either cerium (IV) ammonium sulfate (Method A) or potassium persulfate (Method B). The products of oxidation in both methods are coupled with 3-methylbenzothiazolin 2-one hydrazone, producing a deep blue color with a maximum absorption wavelength at 630 nm. In Method A, the absorbance-concentration plots were linear over the ranges of 5-50 and 10-60 microg/mL with detection limits of 0.18 microg/mL (8 x 10(-7) M) and 0.63 microg/mL (2.58 x 10(-6) M) for ACV and RBV, respectively. In Method B, the ranges were 5-45 and 20-50 microg/mL with detection limits of 0.11 microg/mL (4.88 x 10(-7) M) and 1.40 microg/mL (5.73 x 10(-6) M) for the 2 drugs, respectively. The molar absorptivities were 4.1 x 10(3) and 3.65 x 10(3) L/mol/cm in Method A and 5.03 x 10(3) and 3.97 x 10(3) L/mol/cm in Method B for the 2 drugs, respectively. The proposed methods were applied successfully for the determination of the 2 drugs in their pharmaceutical formulations. The percentage recoveries +/- standard deviation were 99.57 +/- 0.86 and 100.82 +/- 0.46 for ACV; 99.41 +/- 1.08 and 100.35 +/- 1.03 for RBV. The results obtained were compared statistically with those given by official methods and showed no significant differences regarding accuracy and precision.     

Spectrophotometric methods for determination of enalapril and timolol in bulk and in drug formulations

Two simple and accurate spectrophotometric methods for determination of timolol and enalapril maleate are described. The first method is based on chelate formation with palladium(II) chloride in buffered medium. The second method is based on the formation of the colored complex between palladium(II), eosin, and the two cited drugs using methylcellulose as surfactant to increase the solubility and intensity of the formed complexes. Under optimum conditions the complexes showed maximum absorption at 369.4 nm and 362.8 nm for timolol and enalapril maleate, respectively, in the first method and 552.2 and 550.6 nm for the second method. Apparent molar absorptivities were 1.8 x 10(3) and 1.3 x 10(3) and Sandell's sensitivities were 5.9 x 10(-4) and 2.7 x 10(-4) for timolol and enalapril maleate in the first method; in the second method molar absorptivities were 2.8 x 10(4) and 1.1 x 10(4) while Sandell's constants were 9.1 x 10(-3) and 2.3 x 10(-3) for timolol and enalapril maleate. The solutions of the complexes obeyed Beer's law in the concentration ranges 20-200 micro g mL(-1) and 50-300 micro g mL(-1) for timolol and enalapril maleate, respectively. In the second method, because the reaction was more sensitive the ranges were reduced to 1.6-16 micro g mL(-1) for timolol 8-56 micro g mL(-1) for enalapril maleate. The proposed methods were applied to the determination of the two drugs in their pharmaceutical formulation.     

HPLC determination of andrographolide in rat whole blood: study on the pharmacokinetics of andrographolide incorporated in liposomes and tablets

A sensitive and simple high-performance liquid chromatographic method with UV detection was developed and validated for the determination of andrographolide in rat whole blood. Carbamazepine was employed as internal standard and the blood sample was extracted with chloroform. Chromatographic separations were achieved on a Chromasil ODS column (250 x 4.6 mm, 5 microm). The mobile phase was consisted of methanol-water (52:48, v/v) and delivered at 0.8 mL/min. The detection wavelength was set at 225 nm. The calibration curve had a good linearity in the range 0.053-530 microg/mL in rat whole blood with its correlation coefficient being 0.996. The extraction recovery of andrographolide was ranged from 65.7 to 72.6%. The intra-day and inter-days repeatabilities were below 4.2% in terms of the percentage of relative standard deviation (RSD). The method was used to provide data on the pharmacokinetics of the drug in rats. The data obtained was processed using the 3P87 pharmacokinetic program. The results showed that the disposition of andrographolide after intravenous administration of liposomal andrographolide conformed to a two-compartment open model with alpha = 4.75 x 10(-2) +/- 2.41 x 10(-3) min(-1), beta = 3.16 x 10(-3) +/- 1.58 x 10(-4) min(-1), V(c) = 174.67 +/- 13.97 mL, k(21) = 1.60 x 10(-2) +/- 8.12 x 10(-4) min(-1), k(10) = 9.38 x 10(-3) +/- 5.62 x 10(-4) min(-1), k(12) = 2.53 x 10(-2) +/- 1.27 x 10(-3) min(-1) and AUC(0-infinity) = 1525.47 +/- 92.35 microg min/mL. For the intragastric administration of andrographolide tablets, the disposition of andrographolide followed a one-compartment open model with k(e) = 6.78 x 10(-3) +/- 3.53 x 10(-4) min(-1), k(a) = 3.69 x 10(-2) +/- 4.68 x 10(-3) min(-1), T(max) = 59.69 +/- 3.61 min, C(max) = 1.62 +/- 0.11 microg/mL, V(c) = 1056.90 +/- 83.42 mL, AUC(0-infinity) = 348.75 +/- 24.41 microg min/mL.     

Therapeutic Efficacy of Sesquiterpene Farnesol in Treatment of Cutibacterium acnes-Induced Dermal Disorders

Acne vulgaris is a highly prevalent skin disorder requiring treatment and management by dermatologists. Antibiotics such as clindamycin are commonly used to treat acne vulgaris. However, from both medical and public health perspectives, the development of alternative remedies has become essential due to the increase in antibiotic resistance. Topical therapy is useful as a single or combined treatment for mild and moderate acne and is often employed as maintenance therapy. Thus, the current study investigated the anti-inflammatory, antibacterial, and restorative effects of sesquiterpene farnesol on acne vulgaris induced by Cutibacterium acnes (C. acnes) in vitro and in a rat model. The minimum inhibitory concentration (MIC) of farnesol against C. acnes was 0.14 mM, and the IC₅₀ of 24 h exposure to farnesol in HaCaT keratinocytes was approximately 1.4 mM. Moreover, 0.8 mM farnesol exhibited the strongest effects in terms of the alleviation of inflammatory responses and abscesses and necrotic tissue repair in C. acnes-induced acne lesions; 0.4 mM farnesol and clindamycin gel also exerted similar actions after a two-time treatment. By contrast, nearly doubling the tissue repair scores, 0.4 mM farnesol displayed great anti-inflammatory and the strongest reparative actions after a four-time treatment, followed by 0.8 mM farnesol and a commercial gel. Approximately 2–10-fold decreases in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, found by Western blot analysis, were predominantly consistent with the histopathological findings and tissue repair scores. The basal hydroxypropyl methylcellulose (HPMC) gel did not exert anti-inflammatory or reparative effects on rat acne lesions. Our results suggest that the topical application of a gel containing farnesol is a promising alternative remedy for acne vulgaris.     

Development of a novel method based on liquid chromatography-evaporative light scattering detection for the direct determination of streptomycin and dihydrostreptomycin in raw materials, pharmaceutical formulations, culture media and plasma

A novel method for the non-derivatization liquid chromatographic determination of streptomycin (STR) and dihydrostreptomycin (DHSTR) was developed and validated based on evaporative light scattering detection (ELSD). Utilizing a ThermoHypersil BetaBasic C18 analytical column, evaporation temperature of 50 degrees C and pressure of nebulizing gas (nitrogen) of 3.5 bar, the optimized mobile phase was 1.25 mL L(-1) TFA aqueous solution, in an isocratic mode at a rate of 1.0 mL min(-1). STR was eluted at 5.6 min and DHSTR at 7.8 min with a resolution of 4.4. Linear calibration curves were obtained from 2 to 120 microg mL(-1) (r > 0.9990) for STR and 2-75 microg mL(-1) (r > 0.9994) for DHSTR, with a LOD equal to 0.7 and 0.5 microg mL(-1), respectively. The developed method was applied for the assay of STR and DHSTR (sulfate) in pharmaceutical raw materials and formulations, while the simultaneous direct determination of sulfate was feasible (tR = 2.5 min, LOD = 1.4 microg mL(-1), double logarithmic calibration curve in the range of 4-50 microg mL(-1), r > 0.9998). Modified isocratic mobile phase (H2O-ACN, 90:10, v/v, containing 1.25 mL L(-1) TFA), was used for the determination of streptomycin B impurity in STR sulfate raw material and a gradient mobile phase (H2O-ACN containing TFA) was used for the determination of DHSTR in the presence of penicillinG procaine. The developed method was also applied for the assay of commercial formulations (STR powder and DHSTR injection solution and suspension) (%recovery 98-102, %RSD < 1.3, n = 3 x 3), for the determination of STR in bacteria culture medium (%recovery 99.6, %RSD = 0.8, n = 3 x 3), and for the determination of DHSTR in human plasma (2.0-23.0 microg mL(-1)) after solid phase extraction using carboxylate cartridges (%recovery 98.4-101.8, %RSD = 3.2, n = 3 x 3).     

Spectrophotometric flow injection determination of l-ascorbic acid with a packed reactor containing ferric hydroxide

A flow injection system with spectrophotometric detection is proposed for determining l-ascorbic acid in pharmaceutical formulations. In this system a column containing Fe(OH)(3) immobilized in polyester resin (packed reactor) is inserted before the detector. Fe(III)-1,10-phenanthroline complex is reduced by l-ascorbic acid to produce Fe(II)-1,10-phenanthroline complex which is monitored at 510 nm. Under the optimum analytical conditions, the linearity of the calibration equation for l-ascorbic acid ranged from 5.0x10(-6) to 6.0x10(-5) M of added amount. The detection limit was 5.0x10(-7) M and recoveries between 98.5-102.0% were obtained. No interference was observed from the common excipients of pharmaceutical formulations and other active substances such as acetylsalicylic acid, caffeine and thiamine.