2015 Vol. 5, No. 5

Display Method:
Application of analytical instruments in pharmaceutical analysis
2015, 5(5): Ⅰ-Ⅳ.
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Abstract:
LCMS-8050 Continuing the evolution of Shimadzu's UF technology, Shimadzu introduces the LCMS-8050 triple quadrupole mass spectrometer, offering unparalleled measurement speeds and high-sensitivity performance.
Species authentication and geographical origin discrimination of herbal medicines by near infrared spectroscopy:A review
Zhiguo Yu
2015, 5(5): 277-284. doi: 10.1016/j.jpha.2015.04.001
Abstract:
Near infrared (NIR) spectroscopy as a rapid and nondestructive analytical technique, integrated with chemometrics, is a powerful process analytical tool for the pharmaceutical industry and is becoming an attractive complementary technique for herbal medicine analysis. This review mainly focuses on the recent applications of NIR spectroscopy in species authentication of herbal medicines and their geo-graphical origin discrimination.
Four new degradation products of doxorubicin:An application of forced degradation study and hyphenated chromatographic techniques
Dheeraj Kaushik, Gulshan Bansal
2015, 5(5): 285-295. doi: 10.1016/j.jpha.2015.05.003
Abstract:
Forced degradation study on doxorubicin (DOX) was carried out under hydrolytic condition in acidic, alkaline and neutral media at varied temperatures, as well as under peroxide, thermal and photolytic conditions in accordance with International Conference on Harmonization (ICH) guidelines Q1(R2). It was found extremely unstable to alkaline hydrolysis even at room temperature, unstable to acid hy-drolysis at 80 °C, and to oxidation at room temperature. It degraded to four products (O-I-O-IV) in oxidative condition, and to single product (A-I) in acid hydrolytic condition. These products were re-solved on a C8 (150 mm × 4.6 mm, 5μm) column with isocratic elution using mobile phase consisting of HCOONH4 (10 mM, pH 2.5), acetonitrile and methanol (65:15:20, / / ). Liquid chromatography-pho-todiode array (LC-PDA) technique was used to ascertain the purity of the products noted in LC-UV chromatogram. For their characterization, a six stage mass fragmentation (MS6) pattern of DOX was outlined through mass spectral studies in positive mode of electrospray ionization (+ESI) as well as through accurate mass spectral data of DOX and the products generated through liquid chromato-graphy-time of flight mass spectrometry (LC-MS-TOF) on degraded drug solutions. Based on it, O-I-O-IV were characterized as 3-hydroxy-9-desacetyldoxorubicin-9-hydroperoxide, 1-hydroxy-9-desacetyldox-orubicin-9-hydroperoxide, 9-desacetyldoxorubicin-9-hydroperoxide and 9-desacetyldoxorubicin, re-spectively, whereas A-I was characterized as deglucosaminyl doxorubicin. While A-I was found to be a pharmacopoeial impurity, all oxidative products were found to be new degradation impurities. The mechanisms and pathways of degradation of doxorubicin were outlined and discussed.
Multiple responses optimization in the development of a headspace gas chromatography method for the determination of residual solvents in pharmaceuticals
Carla M. Teglia, Milagros Montemurro, María M. De Zan, María S. Cámara
2015, 5(5): 296-306. doi: 10.1016/j.jpha.2015.02.004
Abstract:
An efficient generic static headspace gas chromatography (HSGC) method was developed, optimized and validated for the routine determination of several residual solvents (RS) in drug substance, using a strategy with two sets of calibration. Dimethylsulfoxide (DMSO) was selected as the sample diluent and internal standards were used to minimize signal variations due to the preparative step. A gas chroma-tograph from Agilent Model 6890 equipped with flame ionization detector (FID) and a DB-624 (30 m × 0.53 mm i.d., 3.00μm film thickness) column was used. The inlet split ratio was 5:1. The influ-encing factors in the chromatographic separation of the analytes were determined through a fractional factorial experimental design. Significant variables: the initial temperature (IT), the final temperature (FT) of the oven and the carrier gas flow rate (F) were optimized using a central composite design. Response transformation and desirability function were applied to find out the optimal combination of the chromatographic variables to achieve an adequate resolution of the analytes and short analysis time. These conditions were 30 °C for IT, 158 °C for FT and 1.90 mL/min for F. The method was proven to be accurate, linear in a wide range and very sensitive for the analyzed solvents through a comprehensive validation according to the ICH guidelines.
Application of RP-HPLC method in dissolution testing and statistical evaluation by NASSAM for simultaneous estimation of tertiary combined dosages forms
Yogesh Upadhyay, Nitin Sharma, G.S. Sarma, Ravindra K. Rawal
2015, 5(5): 307-315. doi: 10.1016/j.jpha.2014.11.001
Abstract:
A dissolution method with robust high performance liquid chromatographic (HPLC) analysis for im-mediate release tablet formulation was developed and validated to meet the requirement as per Inter-national Conference on Harmonization (ICH) and United States Food and Drug Administration (USFDA) guidelines. The method involved the use of Agilent ZORBAX Eclipse XDB C18 column, and temperature was maintained at 30 °C. After optimization, the mobile phase was selected as phosphate buffer (KH2PO4, 30 mM):ACN (60:40, v/v) with pH 3.0, and retention time Rt was found as 3.24, 4.16, and 2.55 min for paracetamol (PCM), chlorpheniramine maleate (CPM) and phenylephrine hydrochloride (PH) respec-tively at 265 nm and at a flow rate of 1 mL/min. The relative standard deviation (%RSD) for 6 replicate measurements was found to be less than 2%. Furthermore net analyte signal standard addition method (NASSAM) with spectrophotometer was performed for standard and liquid oral suspension. On the basis of selectivity, sensitivity and accuracy analysis, it was confirmed that this novel method could be useful for simultaneous estimation of the given drug combinations. Two-way analysis of variance (ANOVA) was applied for evaluating the statistical difference between the assay results obtained via both NASSAM and RP-HPLC methods and ultimately no significant difference was found between both the methods. All the methods and results were acceptable and confirmed that the method was suitable for intended use.
High-sensitivity simultaneous liquid chromatography-tandem mass spectrometry assay of ethinyl estradiol and levonorgestrel in human plasma
Abhishek Gandhi, Swati Guttikar, Priti Trivedi
2015, 5(5): 316-326. doi: 10.1016/j.jpha.2015.02.002
Abstract:
A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether: n-hexane (50:50, v/v) solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex C18 (50 mm × 4.6 mm, 2.6μm) column with a mobile phase of 0.1% (v/v) formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.
Determination of atractylon in rat plasma by a GC-MS method and its application to a pharmacokinetic study
Han Yan, Yuanyuan Sun, Yuying Ma, Bin Ji, Xiaohong Hou, Zhiguo Yu, Yunli Zhao
2015, 5(5): 327-331. doi: 10.1016/j.jpha.2015.03.002
Abstract:
A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC-MS) was developed and validated for the determination of atractylon in rat plasma. Plasma samples were processed by liquid-liquid extraction with ethyl acetate-n-hexane (1:1, v/v) using acetophenone as an internal standard (IS). Analytes were determined in selective ion monitoring (SIM) mode using target ions at m/z 108.1 for atractylon and m/z 105.1 for acetophenone. The calibration curve was linear over the concentration range of 10-1000 ng/mL with lower limit of quantification of 10 ng/mL. The intra- and inter-day precision variations were not more than 10.4% and 9.6%, respectively, whilst accuracy values ranged from -6.5% to 4.9%. Extraction recovery of the assay was satisfactory. This method was suc-cessfully applied to quantification and pharmacokinetic study of atractylon in rat plasma after in-tragastric administration of Atractylodis extract.
Rapid screening and distribution of bioactive compounds in different parts of Berberis petiolaris using direct analysis in real time mass spectrometry
Awantika Singh, Vikas Bajpai, Mukesh Srivastava, Kamal Ram Arya, Brijesh Kumar
2015, 5(5): 332-335. doi: 10.1016/j.jpha.2015.05.002
Abstract:
Berberis petiolaris Wall. ex G. Don, an unexplored medicinal plant belonging to the family Berberidaceae, is a large deciduous shrub found in Western Himalaya between 1800-3000 m. Chemical profiling of fruit, leaf, root and stem was done by direct analysis in real time mass spectrometry followed by multivariate analysis for discrimination among the plant parts. The bioactive compounds, including magnoflorine, berberine, jatrorrhizine, thalifendine/berberrubine, demethyleneberberine, reticuline, 8-oxoberberine, N-methyltetrahydroberberine, tetrahydropalmatine, tetrahydroberberine and palmatine, were identified by their exact mass measurement and the corresponding molecular formula of each compound. A comparative study of distribution pattern for all these bioactive alkaloids showed qualitative and quantitative variations in different parts of B. petiolaris. Principal component analysis clearly dis-criminated each part of B. petiolaris plant.