Stability-indicating High-performance Liquid Chromatographic Assay Research Articles

The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at 'high-end' clinical concentrations and physically incompatible with 16 drugs and six '2-in-1' parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters.

Stability of extemporaneously compounded 5-fluorouracil utilizing high performance liquid chromatography.

The goal of the current study is to determine stability of compounded 5-fluorouracil (5-FU) in Intravia™ bags and CADD™ cassettes stored up to 15 days under refrigeration (2-8°C) and room temperature (25°C with 60% relative humidity), with four different concentrations (20 mg/mL, 30 mg/mL, 40 mg/mL, and 50 mg/mL) and two diluents (0.9% sodium chloride and 5% dextrose). A stability-indicating high-performance liquid chromatography (HPLC) method was developed to analyze the 5-FU concentrations. The stability of compounded 5-FU infusions was investigated using this method. Two samples from each storage condition were assessed for stability on days 0, 4, 7, 10, and 15 as per United States Pharmacopeia (USP) guidelines. The assay of 5-FU was done utilizing a calibrated stability-indicating HPLC method. The stability-indicating HPLC assay showed 5-FU completely degraded within 1 hour in basic conditions. No cloudiness or color change was observed during the stability study. Precipitation was observed in the CADD™ cassettes at day 15 in both storage conditions and at day 10 in a single room-temperature CADD™ cassette for 40 mg/mL in 5% dextrose (D5W). HPLC assay revealed the infusions in CADD™ cassettes retained greater than 90% of the initial concentrations of 5-FU for 15 days stored at room temperature (25°C and 60% relative humidity) and for 10 days at refrigeration (2-8°C). Intravia™ bags retained stability through 15 days for all the compounded 5-FU concentrations and both the storage conditions. 5-FU infusions in both CADD™ cassettes and Intravia™ bags were stable for extendable periods in multiple concentrations compared to recommended guidelines for hospital use.

Stability-indicating HPLC method to determine the stability of extemporaneously prepared vancomycin oral solution cups.

To determine the stability of compounded sweetened vancomycin oral formulations in plastic unit dose cups stored up to 180 days under 2 temperature conditions: refrigeration (2°C-6°C) and room temperature (25°C with 60% relative humidity). A stability-indicating high-performance liquid chromatography (HPLC) method was developed to analyze vancomycin in the presence of degradation peaks. The stability of extemporaneously compounded vancomycin solution stored in oral unit dose cups was investigated using this method. The tested vancomycin oral solutions were compounded formulations of 125 mg/2.5 mL and 500 mg/10 mL. Three oral unit dose cups from each storage condition were withdrawn and assessed for stability on days 0, 3, 7, 15, 22, 30, 90, 120, 150, and 180 as per United States Pharmacopeia guidelines. The assay of vancomycin was carried out by using a calibrated stability-indicating HPLC method. The stability-indicating HPLC assay showed that vancomycin completely degraded within 2 hours when exposed to highly acidic or basic pH conditions. No precipitation, cloudiness, or color changes were observed during the study under either temperature condition. The HPLC assay revealed that vancomycin oral solution cups retained greater than 90% of the initial concentrations of vancomycin for 30 days when stored at room temperature (25°C and 60% relative humidity) and for 180 days with refrigeration (2°C-6°C). Vancomycin oral formulations were stable for long-term storage periods beyond those specified in manufacture guidelines. Our data suggests the extended stability of vancomycin oral solutions compounded for hospital use can be extended.

Stability of 10-mg/mL and 50-mg/mL ketamine oral solutions.

Ketamine is an anesthetic agent commonly used for the induction of anesthesia. Ketamine is also given to control pain, for treatment of posttraumatic stress disorder, and to induce bronchodilation in refractory asthma. Moreover, ketamine therapy is gaining ground as an intervention for patients with treatment-resistant depression and individuals who have depression with serious suicidal ideation. Recently, the drug has been used to disrupt maladaptive reward memories in individuals with harmful alcohol consumption behaviors. The stability of 10-mg/mL and 50-mg/mL ketamine solutions stored at ambient and refrigeration temperatures was assessed over 90 days. Three batches of 10-mg/mL and 50-mg/mL ketamine solutions were stored for 90 days under two temperature conditions (2°C-8°C and 22°C-25°C) in amber plastic bottles. Chemical stability was assessed using a stability-indicating high-performance liquid chromatography assay. At each study time, visual inspection and pH assessments of ketamine concentration and pH were conducted. For all solutions tested at each condition, the ketamine concentration remaining was at least 98% of the initial concentration over 90 days of storage. Throughout the study period, solution pH remained stable and the color and odor of the suspensions remained unchanged. Extemporaneously compounded 10-mg/mL and 50-mg/mL oral solutions of ketamine prepared in a flavored suspending excipient and stored in amber polypropylene plastic bottles were stable for at least 90 days at both ambient and refrigeration temperatures.

Stability-indicating high-performance liquid chromatographic assay methods for drugs in pharmaceutical dosage forms: Part I

A review of applications of stability-indicating high-performance liquid chromatographic (HPLC) assay methods for drugs in various pharmaceutical dosage forms is presented. A survey of articles primarily on the significant developments in this field is covered in this paper. Selected substances are grouped to integrate drugs that share similar uses or actions. Papers selected by the authors are briefly summarized, and HPLC systems developed in these papers for stability testing of pharmaceuticals are tabulated to assist readers in selecting an appropriate system for a given pharmaceutical. The information given in the table includes the drug names, materials, column types, mobile-phase compositions, detections, internal standards used and the literature references.

Stability-indicating High-Performance Liquid Chromatographic assay methods for drugs in pharmaceutical dosage forms: Part II

Stability-indicating High-Performance Liquid Chromatographic assay methods for drugs in pharmaceutical dosage forms: Part II

Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions.

Peritonitis is a common and serious complication of peritoneal dialysis (PD). PD-associated peritonitis (PDAP) caused by Pseudomonas is usually resistant to most antibiotics, resulting in high failure rates. Ceftolozane/tazobactam (C/T) has been shown to be effective in treating urinary tract and intra-abdominal infections caused by beta-lactam resistant Pseudomonas and other gram-negative bacteria. Given its favourable adverse effects profile, it has a potential role in the treatment of PDAP caused by Pseudomonas species resistant to other antibiotics. Intraperitoneal administration of antibiotics admixed with PD solutions for the treatment of PDAP is associated with superior outcomes. However, there is a lack of published data on the stability of C/T in PD solutions. Therefore, this study investigated the physical and chemical stability of C/T in commonly used PD solutions at different temperatures. A total of 27 PD bags (3 PD bags for each type of PD solution including Dianeal®, Extraneal®, Balance® and Physioneal® PD bags) containing C/T were prepared and stored at 25°C for 6 h, followed by 4°C for 168 h and then 37°C for 12 h. An aliquot from each PD bag was withdrawn, and the concentration of C/T before (0 h) and after predefined time points was determined using a stability-indicating high-performance liquid chromatography assay. Samples were also assessed for pH, colour change and particulate matter immediately after preparation and on each day of analysis. C/T retained more than 97% of their initial concentration when stored at 25°C for 6 h followed by storage at 4°C for 168 h and then at 37°C for 12 h. Particle formation was not detected at any time under the tested storage conditions. The pH and colour remained essentially unchanged throughout the study. These results provide a platform for clinical studies to determine the safety and therapeutic efficacy of intraperitoneal C/T for the treatment of PDAP caused by resistant Pseudomonas species.

A validated stability-indicating HPLC assay method for Meclizine HCl in bulk drug

An isocratic reversed phase stability-indicating high-performance liquid chromatographic (HPLC) assay method was developed and validated for quantitative determination of Meclizine HCl in bulk drugs. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using a Water Nova Pack C18 (250 x 4.6) mm, 5? column and the mobile phase containing 1.0 gm Sodium dihydrogen phosphate and 1.0 gm 1-octaneSulfonic acid salt in 1000ml water filter and mixed. Prepare a homogenous mixture of buffer, methanol and acetonitile. The detection was carried out at wavelength 264 nm. The developed method was validated with respect to linearity, accuracy (recovery), precision, system suitability, selectivity, robustness prove the stability indicating ability of the method.

Stability of tacrolimus injection diluted in 0.9% sodium chloride injection and stored in Excel bags.

The chemical stability and physical compatibility of tacrolimus i.v. infusion solutions prepared in Excel bags and stored at 23 or 4 °C for up to nine days were studied. Tacrolimus admixtures (2, 4, and 8 μg/mL) were prepared in Excel bags using 0.9% sodium chloride injection and stored at 23 °C without protection from light or at 4 °C in the dark. Test samples were withdrawn from triplicate bag solutions immediately after preparation and at predetermined time intervals (1, 3, 5, 7, and 9 days). Chemical stability was assessed by measuring tacrolimus concentrations using a validated stability-indicating high-performance liquid chromatography assay. The physical stability of the admixtures was assessed by visual examination and by measuring turbidity, particle size, and drug content. All test solutions stored at 23 or 4 °C had a no greater than 6% loss of the initial tacrolimus concentration throughout the nine-day study period. All test samples of tacrolimus admixtures, under both storage conditions, were without precipitation and remained clear initially and throughout the nine-day observation period. Changes in turbidities were minor; measured particulates remained few in number in all samples throughout the study. Extemporaneously prepared infusion solutions of tacrolimus 2, 4, and 8 μg/mL in 0.9% sodium chloride injection in Excel bags were chemically and physically stable for at least nine days when stored at room temperature (23 °C) without protection from light and when stored in a refrigerator (4 °C) in the dark.

Stability-Indicating High-Performance Liquid Chromatography Assay for the Determination of Sulthiame in Pharmaceutical Dosage Forms.

A stability-indicating assay by reversed-phase high performance liquid chromatography method was developed and validated for the determination of sulthiame (STM). The chromatographic separation was achieved on a reversed-phase NovaPack C18 column and an isocratic mobile phase consisting of deionized water:methanol (70:30, v/v). The flow rate was 1.0 mL/min (ultraviolet detection at 210 nm). The STM was separated within 2.83 min. The linearity of the method was demonstrated in the range of 20.0–200.0 μg/mL and a coefficient of determination of r2 = 0.9999. The limits of detection and quantification were 4.2 and 9.5 μg/mL, respectively. The intraday and interday precisions were less than 1%. Accuracy of the method ranged from 98.3% to 101.7%, with a relative standard deviation of <1%. STM was degraded by accelerated breakdown in alkaline, acidic, or oxidative stress conditions. This method allows accurate and reliable determination of STM for drug stability assay in pharmaceutical studies.

Beyond-use date determination of buprenorphine buccal solution using a stability-indicating high-performance liquid chromatographic assay.

The objectives of this study included developing and validating a stability-indicating high-performance liquid chromatographic (HPLC) method with ultraviolet (UV) detection for the determination of buprenorphine in a buccal solution for veterinary use, and applying that method to determine the stability of a 3 mg/ml buprenorphine preparation in room temperature and refrigerated storage conditions. This preparation, intended for buccal administration in feline patients, plays an important role in pain management in cats. A stability-indicating HPLC method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity and robustness based on US Pharmacopeia (USP) General Chapter <1225>. The method was then applied to the study of potency changes over 90 days in a buccal buprenorphine solution stored at two temperatures. All HPLC-UV method data met acceptable criteria for the quantification of buprenorphine in a buccal solution formulation. The buprenorphine concentrations found in each stability sample remained within the 90-110% of label claim throughout the 90 days of study. All stability test bottles of the buprenorphine buccal solution retained their original appearance. For the room temperature bottles, some white particulate matter was noted in the threads of the container bottles starting at day 21. The pH of the preparations during the course of the study was in the range of 3.57-4.06 and 4.01-4.16 for the room temperature and refrigerated samples, respectively. Pharmacists have compounded a concentrated 3 mg/ml buccal solution to use easily in the home care or outpatient setting for treatment of feline pain. Prior to this investigation, pharmacists empirically assigned beyond-use dates to this formulation based on standards in USP General Chapter <795> Pharmaceutical Compounding - Nonsterile Preparations. This study of a 3 mg/ml buprenorphine buccal solution indicates stability through 90 days.

Development and Validation of Rapid Stability-Indicating RP-HPLC-DAD Method for the Quantification of Lapatinib and Mass Spectrometry Analysis of Degraded Products.

A rapid, simple and stability-indicating high-performance liquid chromatography assay method was developed and validated for quantitative analysis of lapatinib (LPT) in bulk pharmaceuticals. The newly developed method was assessed using a C18 MZ-Analytical column (5 µm, 150 × 4.6 mm, OSD-3), which was protected by a (5 µm, 4.0 × 4.6 mm, OSD-3) pre-column with mobile phase that was composed of acetonitrile and water (70/30, v/v) and a detection wave length of 227 nm. The method was validated according to the ICH guidelines with respect to precision, accuracy, linearity, robustness, specificity and system suitability. Forced degradation studies were also performed for LPT to determine the stability-indicating aspect of developed method. The method was found to be specific for LPT in the presence of degradation products. The retention time of LPT was ∼4 min. Accuracy of the method was found to be 2.20% bias for all tested samples. The inter- and intra-day precision of the novel method were found to be 2.84 and 2.78%, respectively. The calibration curve was linear over the concentration range of 5-80 µg/mL with a regression coefficient of 0.9990. The limits of detection and quantification were also found to be 1 and 5 µg/mL, respectively. Mass spectrometry analysis was performed in order to better characterize degraded products.

Validated Stability-Indicating HPLC and UPLC Assay Methods for the Determination of Entacapone in Pharmaceutical Dosage Forms

In the present study, new isocratic stability-indicating reverse phase chromatographic methods were developed using HPLC and UPLC systems for the determination of entacapone (ENT) in its pharmaceutical dosage forms. Ultra performance liquid chromatography (UPLC) using small sub-2 μm particles and high-performance liquid chromatography (HPLC) were compared for separation and determination of the ENT using Acquity HSS C18 (50 × 2.1 mm, 1.8 µm) and Xbridge C18 (150 × 4.6 mm, 5.0 µm) columns by UPLC and HPLC, respectively. When using UPLC, the run time could be reduced five fold and actually the solvent consumption decreased 10 times. The proposed UPLC method would decrease the consumption of organic solvents and reagents. The present methods were validated according to ICH guideline. All analytical procedures including sample preparation, flow rate, run time of the analytical systems were at low levels. Forced degradation studies were also performed for both compounds in bulk drug samples to demonstrate the specificity and stability-indicating comparative advantage of both methods.

Stability of penicillin G sodium diluted with 0.9% sodium chloride injection or 5% dextrose injection and stored in polyvinyl chloride bag containers and elastomeric pump containers

The stability of penicillin G sodium solutions stored in polyvinyl chloride (PVC) bags or elastomeric pump containers was studied. Test samples were prepared by diluting powdered penicillin G sodium (10 million units/10-mL vial) to solutions of 2,500 or 50,000 units/mL with 0.9% sodium chloride injection or 5% dextrose injection. The preparations were transferred to 250-mL PVC bags and elastomeric pump containers. All samples were prepared in triplicate and stored at 5°C. Chemical stability was measured by a stability-indicating high-performance liquid chromatographic (HPLC) assay and by pH evaluation. Particulate matter was evaluated according to compendial standards using a light-obscuration particle count test. Preparations were visually examined throughout the study. After 21 days of storage, all test samples remained chemically stable, with an HPLC assay recovery value of more than 90% of the initial value. After 28 days, all samples prepared with either diluent and stored in PVC bags, as well as the samples diluted to 2,500 units/mL with sodium chloride injection and stored in elastomeric pump containers, did not meet the recovery acceptance limit. For all test samples, the mean pH consistently decreased during storage, from about 6.4 to about 5.5. Particle counts remained acceptable throughout the study, and no change in appearance was observed. Penicillin G for injection (2,500 and 50,000 units/mL) diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored at 5°C in PVC containers or elastomeric pump containers was physically and chemically stable for a period of at least 21 days.

Riluzole: Validation of Stability-Indicating HPLC, D1 and DD1 Spectrophotometric Assays

A stability-indicating reversed-phase high-performance liquid chromatographic assay procedure has been developed and validated for riluzole in the presence of alkaline and oxidative degradation products. The liquid chromatographic separation was achieved and compared isocratically on C18 Zorbax ODS and Poroshell 120 EC-C18 columns by using a mobile phase containing methanol-water, pH = 3.10 (70:30, v/v), at a flow rate of 1 mL/min and ultraviolet detection at 264 nm. The method was linear over the concentration ranges of 20-200 µg/mL (r = 0.9997) and 10-200 µg/mL (r = 0.9995). The limit of detection and quantitation for the two columns were 2 and 6 µg/mL and 1 and 3 µg/mL, respectively. Moreover, spectrophotometric methods were applied for the determination of riluzole in the presence of its oxidative degradation products by using first derivative spectrophotometry at 252.5 and 275.0 nm. The method was linear over the concentration range of 1-20 µg/mL (r = 0.9995 and 0.9996) at the studied wavelengths, with limits of detection and quantitation of 0.1 and 0.3 µg/mL. In addition, the first derivative ratio spectrophotometry (DD1) method was applied for the determination of riluzole in the presence of its alkaline degradation product at 252.0, 278.5 and 306.3 nm by using 100 µg/mL of alkaline degraded riluzole as a divisor; riluzole was additionally determined in the presence of its hydrogen peroxide oxidative degradation products at 252.5, 275.0 and 305.0 nm by using 200 µg/mL of oxidative degraded riluzole as a divisor. The DD1 method was linear over the concentration range of 1-20 µg/mL (r = 0.9996, 0.9995 and 0.9996 for the alkaline degradation product at the three studied wavelengths, respectively; and r = 0.9995, 0.9996 and 0.9995 for the oxidative degradation product at the three studied wavelengths, respectively), with limits of detection and quantitation of 0.1 and 0.3 µg/mL for both alkaline and oxidative degradation products. The two studied chromatographic and spectrophotometric methods were comparable and display the required accuracy, selectivity, sensitivity and precision to assay riluzole in bulk and pharmaceutical dosage forms. Degradation products resulting from the stress studies did not interfere with the detection of riluzole, which indicates that these are stability-indicating assays.

Stability of Ciprofloxacin in Polyvinylchloride Minibags

Ciprofloxacin is a fluoroquinolone antibiotic used to treat infections caused by both gram-positive and gram-negative organisms. To determine the physical and chemical stability of ciprofloxacin diluted in 5% dextrose in water (D5W) or 0.9% sodium chloride (normal saline [NS]) and stored in polyvinylchloride (PVC) minibags at various temperatures. Solutions of ciprofloxacin (1 and 2 mg/mL) were prepared by diluting a commercially available concentrate (10 mg/mL) with either D5W or NS. The prepared solutions were then packaged in PVC mini-bags. Three minibags of each concentration-diluent combination were stored at 2°C to 8°C with protection from light, at 21°C to 24°C with exposure to light, and at 29°C to 31°C with protection from light. Samples were collected from each minibag on days 0, 7, 14, and 30 and then analyzed. Colour, clarity, and pH were monitored when the samples were collected. On each day of analysis, the samples were accurately diluted before duplicate analysis with a stability-indicating high-performance liquid chromatography assay. A solution was considered stable if the concentration remained above 90% of the initial values. There were no changes in the physical characteristics of any of the solutions. At both concentrations (1 and 2 mg/mL), the ciprofloxacin solutions prepared in D5W remained above 93.9% of the initial concentration over the 30-day study period under all 3 storage conditions. Similarly, at both concentrations, solutions diluted in NS remained above 95.9% of the initial concentration over the 30-day study period under all 3 storage conditions. Ciprofloxacin prepared in either D5W or NS and stored in PVC minibags was stable for 30 days under 3 separate storage conditions: 2°C to 8°C with protection from light, 21°C to 24°C with exposure to light, and 29°C to 31°C with protection from light.

Stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride and polyolefin bags

The stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride (PVC) and polyolefin bags under varying conditions was evaluated. Triplicate solutions of midazolam hydrochloride 1-mg/mL were prepared in polyolefin and PVC i.v. bags by diluting midazolam hydrochloride injection 5 mg/mL with 5% dextrose injection. Bags were then stored under refrigeration (3-4 °C), exposed to light at room temperature (20-25 °C), or protected from light in amber bags at room temperature. Samples were taken immediately after preparation (day 0) and on days 1, 2, 3, 6, 13, 20, and 27 for analysis with a stability-indicating high-performance liquid chromatography assay in order to determine solution concentration. Stability was defined as retention of at least 90% of the initial drug concentration. The pH of each solution was also measured weekly. Sterility of the i.v. bags was determined at the end of the study by microbiological testing with culture in growth media. Differences in concentrations under the various storage conditions and bags used were analyzed using analysis of variance. All solutions retained over 98% of the initial midazolam hydrochloride concentration, with no statistically significant (p ≥ 0.05) change in concentration over the four-week period. Stability was not affected by temperature, exposure to light, or bag type. The pH of all solutions remained between 3.2 and 3.4 throughout the study. Sterility after 28 days was retained. Midazolam hydrochloride 1-mg/mL solutions diluted in 5% dextrose injection remained stable over 27 days in both polyolefin and PVC i.v. bags, regardless of storage condition.

Chemical stability of tramadol hydrochloride injection admixed with selected pain drugs.

Background:Tramadol hydrochloride (HCl) and ketorolac tromethamine are analgesic drugs, which are commonly used in combination in postoperative pain management. According to some studies, metoclopramide and magnesium sulfate (MgSO4) as adjuvant agents can improve analgesia and decrease the need for other pain drugs.Materials and Methods:The chemical stability of tramadol HCl combined with ketorolac tromethamine and metoclopramide HCl has been studied using a stability-indicating high-performance liquid chromatographic assay method. Calibration curves were produced using linear regression of the peak area against concentration of each drug, with an r2 value ≥ 0.96. Our aim was to investigate the stability of admixture solution of tramadol HCl combined with ketorolac tromethamine and metoclopramide HCl for 48 h (25°C) and 5 days (5°C), with MgSO4, which has never been assessed.Results:Data obtained for admixtures prepared and stored at temperatures of 25°C and 5°C, show that all drugs have reached at least 98% of the initial concentration.Conclusions:For the purpose of pre-preparing drug admixtures to use with confidence, tramadol HCl infusions may be prepared in advance and then thawed before use in clinical units. On the basis of our results, the intravenous mixture of tramadol (7.69 mg/mL), metoclopramide (0.19 mg/mL), ketorolac (1.15 mg/mL), and magnesium sulfate (77 mg/mL) may be considered for a possible commercial formulation.

Stability-indicating HPLC determination of pramipexole dihydrochloride in bulk drug and pharmaceutical dosage form

A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for quantitative determination of pramipexole dihydrochloride in bulk drugs and in pharmaceutical dosage form in the presence of degradation products. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using an Ace5-C18 (250×4.6 mm, 5 µm) advance chromatography column, and 10 mmol L-1 ammonium acetate and acetonitrile (75:25 v/v) as a mobile phase. The detection was carried out at a wavelength of 260 nm. The pramipexole was subjected to stress conditions of hydrolysis (acid, base), oxidation, photolysis and thermal degradation. Degradation was observed for pramipexole in base, in acid and in 30% H2O2. The drug was found to be stable in the other stress conditions attempted. The degradation products were well resolved from the main peak. The percentage recovery of pramipexole was from (99.87 to 99.98%) in the pharmaceutical dosage form. The developed method was validated with respect to linearity, accuracy (recovery), precision, system suitability, specificity and robustness. The forced degradation studies prove the stability indicating power of the method.

Stability of docetaxel diluted to 0.3 or 0.9 mg/mL with 0.9% sodium chloride injection and stored in polyolefin or glass containers

The stability of docetaxel diluted to 0.3 or 0.9 mg/mL with 0.9% sodium chloride injection and stored in polyolefin or glass containers was studied. Vials of docetaxel injection concentrate were reconstituted with the entire contents of the solvent vial and carefully homogenized to avoid the formation of foam. Solutions were aseptically prepared with nominal docetaxel concentrations of 0.3 and 0.9 mg/mL by adding the appropriate quantities to polyolefin containers or glass bottles, to which had been added the appropriate volume of 0.9% sodium chloride injection, yielding a final volume of 50 mL. Three identical polyolefin containers and one control glass bottle for each concentration were prepared. All test solutions were stored at 19-21 degrees C and protected from light. Chemical stability was measured by using a stability-indicating high-performance liquid chromatographic (HPLC) assay with ultraviolet-light detection. Physical stability was determined by visual inspection. No evidence of precipitation was observed during the first 24 hours of the study. However, after a day of storage, the HPLC assay revealed large relative standard deviation values for diluted docetaxel solutions in some containers. These values were predictive for the formation of precipitates and compatible with the existence of microprecipitates at 24 hours. These results suggest that the diluted docetaxel infusions were not stable when stored at 19-21 degrees C. Docetaxel 0.3 and 0.9 mg/mL in 0.9% sodium chloride injection was not physically stable for more than one day when stored at 19-21 degrees C. Docetaxel stability in diluted solutions appears sensitive to slight changes in temperature and degree of agitation.