Development and validation of an HPLC method for the determination of verapamil residues in supports of cleaning procedure

Analytical method validation, determining the recovery rate from the equipment surface, and stability of a potential contaminant are important steps of a cleaning validation process. An HPLC method for the determination of the verapamil residues on stainless steel surfaces of the equipment employed in drug manufacture is described. The cleaning validation sample impurities as well as excipients of the commercial sample did not interfere in the analysis which proved the selectivity of the method. The validation of the method demonstrated acceptable levels of the linearity, precision and accuracy. Cotton swabs, moistened with methanol were used to remove any residues of drugs from stainless steel surfaces, and give recoveries of above 78.59% for three diferent concentration levels. The precision of the results, reported as the relative standard deviation (RSD, %), were below 1.58%. Low quantities of the drug residues were determined by HPLC using a Hypersil ODS column (125 × 4.0 mm, 5 μm) at 25°C with the mobile phase metanol-water-triethylamine (70: 30: 0.2, v/v/v) at a flow rate of 0.6 mL/min, injection volume of 50 μL and detection at 278 nm.     

Pharmaceutical cleaning validation using non‐proximate large‐area desorption electrospray ionization mass spectrometry

Desorption electrospray ionization (DESI) is a droplet‐based ionization method that is applied to samples in the ambient environment with little or no sample preparation. Its utility for industrial applications is explored here for the case of pharmaceutical cleaning validation. A non‐proximate large‐area DESI system was built to examine representative areas of the surfaces of reaction vessels used in active product ingredient (API) manufacturing. A large‐area sprayer capable of sampling an area of ～2.5 cm² was coupled with a transport tube to allow sensitive, representative sampling of APIs from a stainless steel surface 1 m away from the mass spectrometer. The system was used to detect the APIs neostigmine, acebutolol, amiloride, amiodarone, ibuprofen, montelukast, potassium clavulanate, and β‐estradiol, at levels as low as 30–10 ng/cm², easily satisfying the general acceptable limits set by the pharmaceutical industry. These levels were achieved from surfaces resembling the equipment used in API manufacturing processes at a rate of 30 s per analysis. Copyright © 2008 John Wiley & Sons, Ltd.     

Spray desorption collection: an alternative to swabbing for pharmaceutical cleaning validation

Spray Desorption Collection (SDC) allows for much larger areas of surfaces to be sampled compared to traditional swabbing techniques, providing a valuable pre-concentration advantage. Closely related to desorption electrospray ionization (DESI), analytes from the sample surface are collected onto a selected collection surface, which in a second step can be analyzed directly. Here we demonstrate the application of SDC as a large surface area sampling tool coupled with paper spray MS (PS-MS) and demonstrate its capabilities for cleaning validation of pharmaceutical equipment for both acidic and basic active ingredients from an aluminium surface.     

General method validation guidelines for pharmaceutical samples

Method validation guidelines, which provide an organizational structure for the design and evaluation of a validation procedure, are presented for a wide range of pharmaceutical applications. The validation guidelines are based on the analyte concentration/sample matrix combination to which the method will be applied. These guidelines include the selection of appropriate validation parameters, design considerations for evaluation, and a discussion of acceptance guidelines for the determination of acceptable method performance. A set of tables is included which illustrates the selection and testing procedure and tailors the entire validation process to the specific characteristics of the determination to be made.     

激光粒度分析技术在药物研究和质量控制中的应用进展

近年来,激光粒度分析技术广泛应用于药物的质量研究和质量控制领域.从激光散射测定粒度的原理、仪器的一般要求和影响测试结果的因素、方法验证的要求以及该技术在药物领域中最新应用等方面进行综述,为激光粒度分析技术在药物中的应用开发提供有益的参考.     

Quantitative validation of a flow-injection determination of penicillin in pharmaceutical formulations by means of a validation program based on an expert system

The quantitative validation of the results of a flow-injection determination of penicillin in pharmaceutical formulations is described. The validation procedure is done by using VALID, which is a generally applicable validation program based on an expert system program. The automated penicillin assay is based on the enzymatic hydrolysis of the penicillin to the corresponding penicilloic acid, which reacts with iodine generated on-line; the iodine consumption is detected amperometrically. The method is evaluated for applicability in pharmaceutical quality control. The complete validation procedure is described. During the program run, the system evaluates the calibration procedure, the drift of the analytical systemm and the effect of the sample matrix. The reliability of the flow-injection method is estimated by evaluating the maximum total error (MTE), which includes both random error and systematic error. The latter was assessed by comparing of the results of the flow-injection method with the results obtained by titration with mercury(II) as the reference method. The user requirement for the assay was an MTE of 10%. The validation procedure showed that the analytical method complied with the requirements for the major part of the concentration range (0.066–0.25 mM).     

Validation of a Quantitative Method Determination of Estradiol in Pharmaceutical Products using UV-Vis Molecular Absorption Spectrometry

Abstract

This article describes the development and validation of a quantitative analytical method for determination of estradiol in several pharmaceutical products (powder, tablets, cream, solutions for injection) using UV-vis molecular absorption spectrometry. The proposed method is accurate, precise, sensitive, and selective and can be used in quality control laboratories.     

Quantitative determination and sampling of lamivudine and zidovudine residues for cleaning validation in a production area

Lamivudine (3TC) and zidovudine (AZT) are systemic antiviral substances extensively used in human immunodeficiency virus (HIV) infected patients. Nowadays, 3TC, AZT, and several other pharmacologically potent pharmaceuticals are manufactured in the same production area. To assure quality of drug products and patient safety, properly validated cleaning methodology is necessary. A carefully designed cleaning validation and its evaluation can ensure that residues of 3TC and AZT will not carry over and cross contaminate the subsequent product. The aim of this study was to validate a simple analytical method for verification of residual 3TC and AZT in equipment used in the production area and to confirm the efficiency of the cleaning procedure. The liquid chromatography method was validated using a Nova-Pak C18 column (3.9 x 150 mm, 4 microm particle size) and methanol-water (20 + 80, v/v) as the mobile phase at a flow rate of 1.0 mL/min. Ultraviolet detection was made at 266 nm. The calibration curve was linear over a concentration range of 2.0-22.0 microg/mL with a correlation coefficient of 0.9998. The detection and quantitation limits were 0.36 and 1.21 microg/mL, respectively. The intra-day and interday precision expressed as relative standard deviation were below 2.0%. The mean recovery of the method was 99.19%. The mean extraction recovery from manufacturing equipment was 83.5%.     

Reflectance near-infrared spectroscopic method with Chemometric techniques for simultaneous determination of Chondroitin, glucosamine, and methyl sulfonyl methane

Reflectance near-IR (RNIR) spectroscopy was used for the simultaneous determination of chondroitin (CH), glucosamine (GO), and methyl sulfonyl methane (MSM) in tablets. Simple sample preparation was done by grinding, sieving, and compression of the tablets for improving RNIR spectra. Principal component regression and partial least squares (PLS-1 and PLS-2) were successfully applied to quantify the three components in the studied mixture using information included in RNIR spectra in the range of 4350-9100 cm(-1). The calibration model was developed with drug concentration ranges of 14.5-44.2% (w/w) for CH, 18.4-55.3% (w/w) for GO, and 6-18.6% (w/w) for MSM with addition of tablet excipients to the calibration set in the same ratio as in the tested tablets. The calibration models were evaluated by internal validation, cross-validation, and external validation using synthetic and pharmaceutical preparations. The proposed method was applied for analysis of six batches of the pharmaceutical product. The results of the proposed method were compared with the results of the pharmacopoeial method for the same batch of the pharmaceutical product. No significant differences between the results were found. The RNIR method is accurate and precise, and can be used for QC of pharmaceutical products.     

Reflectance near-infrared spectroscopic method with a chemometric technique using partial least squares multivariate calibration for simultaneous determination of chondroitin, glucosamine, and ascorbic acid

A reflectance near-infrared (RNIR) spectroscopy method was developed for simultaneous determination of chondroitin (CH), glucosamine (GO), and ascorbic acid (AS) in capsule powder. A simple preparation of the sample was done by grinding, sieving, and compression of the powder sample for improving RNIR spectra. Partial least squares (PLS-1 and PLS-2) was successfully applied to quantify the three components in the studied mixture using information included in RNIR spectra in the 4240-9780 cm(-1) range. The calibration model was developed with the three drug concentrations ranging from 50 to 150% of the labeled amount. The calibration models using pure standards were evaluated by internal validation, cross-validation, and external validation using synthetic and pharmaceutical preparations. The proposed method was applied for analysis of two pharmaceutical products. Both pharmaceutical products had the same active principle and similar excipients, but with different nominal concentration values. The results of the proposed method were compared with the results of a pharmacopoeial method for the same pharmaceutical products. No significant differences between the results were found. The standard error of prediction was 0.004 for CH, 0.003 for GO, and 0.005 for AS. The correlation coefficient was 0.9998 for CH, 0.9999 for GO, and 0.9997 for AS. The highly accurate and precise RNIR method can be used for QC of pharmaceutical products.     

A New Chemometric Strategy in Electrochemical Method Optimization for the Quantification of Cefdinir in Tablets,Effervescent Tablets and Suspension Samples

A new voltammetric method, based on the use of single‐use pencil graphite electrode, was developed for the quantitative determination of cefdinir by square wave voltammetry. Chemometric optimization strategy was used to select the suitable values for three experimental parameters (pH of the supporting electrolyte, frequency and square wave amplitude) by applying a 3³ full factorial design model. The optimal voltammetric conditions were found to be pH 5.0 for supporting electrolyte (Britton‐Robinson buffer), 43 mV for square wave amplitude and 108 Hz for frequency. Square wave voltammograms of calibration, validation and unknown samples were recorded between 0.0–1400 mV under the optimized voltammetric conditions. Linear regression equation was computed in the linear working range of 0.5–20 μg/mL by using the relationship between the concentration and peak current at 600 mV. The optimized voltammetric method was validated by assessing the analysis results of validation samples. Then the proposed method was applied for the quantitative determination of cefdinir in three different pharmaceutical preparations, namely film‐coated tablets, effervescent tablets and powder for oral suspension. It was concluded that the proposed voltammetric method was suitable for the quantitative analysis of commercial pharmaceutical preparations containing cefdinir.     

Method validation of modern analytical techniques

 Validation of analytical methods of well-characterised systems, such as are found in the pharmaceutical industry, is based on a series of experimental procedures to establish: selectivity, sensitivity, repeatability, reproducibility, linearity of calibration, detection limit and limit of determination, and robustness. It is argued that these headings become more difficult to apply as the complexity of the analysis increases. Analysis of environmental samples is given as an example. Modern methods of analysis that use arrays of sensors challenge validation. The output may be a classification rather than a concentration of analyte, it may have been established by imprecise methods such as the responses of human taste panels, and the state space of possible responses is too large to cover in any experimental-design procedure. Moreover the process of data analysis may be done by non-linear methods such as neural networks. Validation of systems that rely on computer software is well established. The combination of software validation with validation of the analytical responses of the hardware is the challenge for the analytical chemist. As with validation of automated equipment such as programmable logic controllers in the synthesis of pharmaceuticals, method developers may need to concentrate on the process of validation, as well as the minutiae of what is done.     

High-performance liquid chromatographic determination of amphotericin B in a liposomal pharmaceutical product and validation of the assay

A validated high-performance liquid chromatographic method is presented to quantitate amphotericin B (AB) in a liposomal pharmaceutical formulation. The analysis is based on the chromatographic separation of AB and 1-amino-4-nitronaphthalene (the internal standard) on a C18 muBondapac reversed-phase column with a mobile phase consisting of a mixture of acetonitrile and 0.02 M ethylenediamine tetra-acetic acid disodium salt at pH 5.0 (45:55, v/v). The chromatographic analysis time is less than 10 min, and the validation of the assay shows that it is selective, accurate, and linear for the concentration range of 2.50 to 7.50 microg/mL with a detection limit of 0.00500 microg/mL. The within-day and between-day relative standard deviation values are 1.26% (n = 18) and 1.25% (n = 8), respectively. The method described conforms to the validation of compendial methods used for finished pharmaceutical products in general and offers a reliable, quick, and cost-effective procedure for examining the consistency or quality-control analysis of AB in liposomal products. It can also be applied for the determination of AB in other nonliposomal lipid-based drug delivery systems that are on the market.     

Simultaneous Spectrofluorimetric Determination of Paracetamol and Caffeine in Pharmaceutical Preparations in Solid‐Phase Using Partial Least Squares Multivariate Calibration

Abstract

Partial least‐squares algorithm (PLS)‐1 was used for the solid‐phase spectrofluorimetric determination of paracetamol (PA) and caffeine (CF) in pharmaceutical formulations. In despite of the closely overlapping spectral bands, the method allows the simultaneous quantification and sample preparation prior to analysis is not required. The calibration set consisted of 96 samples with 100–400 mg/g^?1 PA plus 10–65 mg/g^?1 CF; another set of 25 samples was used for external validation. Agreement between predicted and experimental concentrations was fair (r=0.993 and 0.964 for PA and CF models). Prediction performance was evaluated in terms of the coefficient of variability (CV), relative predictive determination (RPD), and ratio error range (RER). The PLS‐1 model was used for the determination of PA and CF in pharmaceutical formulations.     

RP-HPLC Method for the Simultaneous Estimation of Eight Cardiovascular Drugs

The present study describes a convenient method for the separation and simultaneous determination of eight drugs used in cardiovascular diseases, viz., atenolol (ATN), lisinopril (LISI), hydrochlorothiazide (HCTZ), enalapril maleate (ENA), amlodipine besylate (AMLO), losartan potassium (LOSA), valsartan (VAL) and atorvastatin calcium (ATOR) in pharmaceutical formulations. A ZORBAX Rx-C8 column (250 × 4.6 mm, 5 μm particle size) was used with mobile phase consisting of acetonitrile, 10 mM dipotassium hydrogen phosphate buffer (pH 2.2 adjusted with orthophosphoric acid) using a gradient program and quantitative evaluation was performed at 210 nm with a flow rate of 1.0 mL min^?1. Suitability of this method for the quantitative determination of the drugs was proved by validation in accordance with International Conference on Harmonization guidelines. The method is selective, precise, robust, accurate and can be used for routine analysis of 15 combination pharmaceutical formulations in quality control.     

Determination of volatile organic compounds in recycled polyethylene terephthalate and high-density polyethylene by headspace solid phase microextraction gas chromatography mass spectrometry to evaluate the efficiency of recycling processes

A method for the determination of volatile organic compounds (VOCs) in recycled polyethylene terephthalate and high-density polyethylene using headspace sampling by solid-phase microextraction and gas chromatography coupled to mass spectrometry detection is presented. This method was used to evaluate the efficiency of cleaning processes for VOC removal from recycled PET. In addition, the method was also employed to evaluate the level of VOC contamination in multilayer packaging material containing recycled HDPE material. The optimisation of the extraction procedure for volatile compounds was performed and the best extraction conditions were found using a 75 μm carboxen-polydimethylsiloxane (CAR-PDMS) fibre for 20 min at 60 °C. The validation parameters for the established method were linear range, linearity, sensitivity, precision (repeatability), accuracy (recovery) and detection and quantification limits. The results indicated that the method could easily be used in quality control for the production of recycled PET and HDPE.     

Microbiological assay for the determination of telithromycin in tablets

This study describes the development and validation of a microbiological assay, applying the cylinder-plate method, for the determination of the antibiotic telithromycin. The microbiological method consisted of a cylinder-plate agar diffusion assay using Micrococcus luteus ATCC 9341 as the test microorganism. The response graphs for standard and sample solutions were linear (r = 0.9987), and no parallelism deviations were detected in the tested concentrations (0.25, 0.5, and 1.0 microg/mL). The interday precision was 2.67%. Recovery values were between 96.75 and 100.91%. A preliminary stability study of telithromycin showed that the microbiological assay is specific for the determination of telithromycin in the presence of its degradation products. The proposed method allows the quantitation of telithromycin in pharmaceutical dosage form and can be used for drug analysis in routine quality control.     

Development and validation of new assay method for the simultaneous analysis of diltiazem, metformin, pioglitazone and rosiglitazone by RP-HPLC and its applications in pharmaceuticals and human serum

Simple, sensitive, rapid, and accurate high-performance liquid chromatographic (HPLC) method is developed and validated for the simultaneous determination of diltiazem, metformin, pioglitazone, and rosiglitazone hydrochloride in raw materials, their pharmaceutical formulations, and human serum. In HPLC, all the above drugs were chromatographed using acetonitrile-methanol-water (30:20:50, v/v, pH 2.59 ± 0.02) as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The separation is carried out on a Hiber, 250-4.6 RP-18 column, equipped with a UV-vis detector at 230 nm. All the antidiabetic drugs eluted at different retention time and each showed a good resolution from diltiazem. The method is successfully applied to pharmaceutical formulations because no chromatographic interferences from the tablet excipients are found. The method is found to be linear, accurate, and precise with apposite detection and quantification limit. Suitability of the method for the quantitative determination of the drugs is proven by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH) guidelines. The validation results, together with statistical treatment of the data, demonstrated the reliability of this method.     

Simultaneous spectrophotometric determination of pyrantel pamoate and febantel in pharmaceutical preparations using partial least-squares regression

The multivariate spectroscopic determination of the combination of pyrantel pamoate (PP) and febantel (FB) in pharmaceutical preparations was carried out by partial least-squares regression. The UV absorbance spectra of standard mixtures of PP and FB were measured at concentrations ranging from 5.76–11.52 and 6–12 μg/mL, respectively, in a diluent solution of methanol and acetonitrile. The best model was selected with variable selection (280–320, 380–400 nm), 2 latent variables and mean centered. External validation was performed using 13 different mixtures, which provided prediction errors lower than 1%. The method was validated in accordance with international and Brazilian guidelines. This method was successfully employed to quantify the drug content in two different pharmaceutical formulations (solid — capsules, liquid — oral suspensions) with good prediction capacity. Furthermore, its advantages include the use of simple and accessible reagents and equipment, and a low operating cost.