Development of a Sensitive Headspace Gas Chromatography–Mass Spectrometry Method for the Simultaneous Determination of Nitrosamines in Losartan Active Pharmaceutical Ingredients

Wichitnithad, Wisut; Sudtanon, Orawan; Srisunak, Pawadee; Cheewatanakornkool, Kamonrak; Nantaphol, Siriwan; Rojsitthisak, Pornchai

doi:10.1021/acsomega.1c00982

Cited by 37 publications

(16 citation statements)

References 14 publications

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“…A homoscedasticity test was also carried out in a concentration range of 0.1–15 mg/L [ 29 ]. The regression line and homoscedasticity of the calibration curve were assessed in order to establish whether the ordinary or the weighted least square were adequate for the robust calibration model [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

A Stability-Indicating Ultra Performance Liquid Chromato-Graphic (UPLC) Method for the Determination of a Mycophenolic Acid-Curcumin Conjugate and Its Applications to Chemical Kinetic Studies

et al. 2021

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A simple, precise, and accurate reversed-phase ultra-performance liquid chromatographic (UPLC) method was developed and validated for the determination of a mycophenolic acid-curcumin (MPA-CUR) conjugate in buffer solutions. Chromatographic separation was performed on a C18 column (2.1 × 50 mm id, 1.7 µm) with a gradient elution system of water and acetonitrile, each containing 0.1% formic acid, at a flow rate of 0.6 mL/min. The column temperature was controlled at 33 °C. The compounds were detected simultaneously at the maximum wavelengths of mycophenolic acid (MPA), 254 nm, and curcumin (CUR), or MPA-CUR, at 420 nm. The developed method was validated according to the ICH Q2(R1) guidelines. The linear calibration curves of the assay ranged from 0.10 to 25 μg/mL (r2 ≥ 0.995, 1/x2 weighting factor), with a limit of detection and a limit of quantitation of 0.04 and 0.10 μg/mL, respectively. The accuracy and precision of the developed method were 98.4–101.6%, with %CV < 2.53%. The main impurities from the specificity test were found to be MPA and CUR. Other validation parameters, including robustness and solution stability, were acceptable under the validation criteria. Forced degradation studies were conducted under hydrolytic (acidic and alkaline), oxidative, thermal, and photolytic stress conditions. MPA-CUR was well separated from MPA, CUR, and other unknown degradation products. The validated method was successfully applied in chemical kinetic studies of MPA-CUR in different buffer solutions.

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Section: Resultsmentioning

confidence: 99%

A Stability-Indicating Ultra Performance Liquid Chromato-Graphic (UPLC) Method for the Determination of a Mycophenolic Acid-Curcumin Conjugate and Its Applications to Chemical Kinetic Studies

et al. 2021

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“…For instance, gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) − are two main approaches for quantifying N -nitrosamines typically generated during the manufacturing process. Hyphenation of GC with other detectors was also performed for the N -nitrosamine determination in water, such as using GC-FID (flame ionization detector) and GC-NPD (nitrogen–phosphorus detector). − Determination of N -nitrosamines in food products was reported using LC-DAD (diode array detector) and fluorimetric detector . Starting materials, recovered solvents, catalysts, and reagents were recognized as the root sources of N -nitrosamines.…”

Section: Introductionmentioning

confidence: 99%

Absolute Quantitation of N-Nitrosamines by Coulometric Mass Spectrometry without Using Standards

Wang

Liu

et al. 2022

J. Am. Soc. Mass Spectrom.

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Carcinogenic N-nitrosamines were recently found in the sartan family of drugs and caused many drug recalls. Both of their detection and quantification are therefore important. Methods reported for N-nitrosamine quantitation rely on the use of standards and are just applicable to simple N-nitrosamines. There is an urgent need to quantify N-nitrosamines derived from drugs with a complicated structure that lack standards. To tackle the issue, this study describes a novel absolute quantitation strategy for N-nitrosamines using coulometric mass spectrometry (CMS) without standards. In our approach, N-nitrosamine is first converted into electrochemically active hydrazine via zinc reduction under acidic condition and the resulting hydrazine can then be easily quantified using CMS. To validate our method, six simple N-nitrosamines, N-nitrosodiethylamine (NDEA), N-nitroso-4-phenylpiperidine (NPhPIP), N-nitrosodiphenylamine (NDPhA), N-nitrosodibutylamine (NDBA), N-nitrosodipropylamine (NDPA), and N-nitrosopiperidine (NPIP), were chosen as test samples, and they all were quantified with excellent measurement accuracy (quantitation error ≤1.1%). Taking this one step further, as a demonstration of the method utility, a drug-like N-nitrosamine, (R)-N-(2-(6-chloro-5-methyl-1′-nitroso-2,3-dihydrospiro[indene-1,4′-piperidin]-3-yl)propan-2-yl)acetamide (VII), was also synthesized and successfully quantified using our method at 15 ppb level in a complex formulation matrix, following solvent extraction, N-nitrosamine isolation, and reductive conversion. Because of the feature of requiring no standards, CMS provides a simple and powerful approach for N-nitrosamine absolute quantitation and has great potential for analysis of other drug impurities or metabolites.

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“…Therefore, the headspace gas chromatography (HSGC) method is used for the determination of VLE because this method has several advantages such as short VLE time, low dosage of reagents, and accurate temperature control. 18 − 21 …”

Section: Introductionmentioning

confidence: 99%

“…Since both turpentine and rosin contain many components which are not easily separated, VLE data for the turpentine + rosin system measured by the usual method of Ellis and Rose using a double-cycle equilibrium kettle seemed difficult. Therefore, the headspace gas chromatography (HSGC) method is used for the determination of VLE because this method has several advantages such as short VLE time, low dosage of reagents, and accurate temperature control. − …”

Section: Introductionmentioning

confidence: 99%

Measurement and Prediction of Isothermal Vapor–Liquid Equilibrium and Thermodynamic Properties of a Turpentine + Rosin System Using the COSMO-RS Model

Chen

Wang

et al. 2022

ACS Omega

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The vapor–liquid equilibrium (VLE) of components of a turpentine + rosin system were measured at 313.2 and 333.2 K using headspace gas chromatography. The thermodynamic properties of the turpentine + rosin system such as activity coefficients, total pressure, partial pressure, excess Gibbs energies, and excess enthalpies were calculated using the COSMO-RS model. The results showed that the activity coefficients were greater than 1 for all components of turpentine except for longifolene, indicating a positive deviation from Raoult’s law for all components of turpentine except for longifolene. The total pressures were about 1 kPa at 313.2 K and about 3 kPa at 333.2 K. Meanwhile, the excess Gibbs energies G E and excess enthalpies H E of the system were positive, indicating that the mixing of the components of turpentine and rosin was endothermic. Moreover, the hydrogen bonding interaction energy H E (hydrogen bonding) contributed the most for the excess enthalpies H E .

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Development of a Sensitive Headspace Gas Chromatography–Mass Spectrometry Method for the Simultaneous Determination of Nitrosamines in Losartan Active Pharmaceutical Ingredients

Cited by 37 publications

References 14 publications

A Stability-Indicating Ultra Performance Liquid Chromato-Graphic (UPLC) Method for the Determination of a Mycophenolic Acid-Curcumin Conjugate and Its Applications to Chemical Kinetic Studies

A Stability-Indicating Ultra Performance Liquid Chromato-Graphic (UPLC) Method for the Determination of a Mycophenolic Acid-Curcumin Conjugate and Its Applications to Chemical Kinetic Studies

Absolute Quantitation of N-Nitrosamines by Coulometric Mass Spectrometry without Using Standards

Measurement and Prediction of Isothermal Vapor–Liquid Equilibrium and Thermodynamic Properties of a Turpentine + Rosin System Using the COSMO-RS Model

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