Detection of 14 sulfonate esters impurities of active pharmaceutical ingredients based on GC-MS/MS and LC-MS/MS / 药学学报

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL-1 and 9-150 ng·mL-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L-1 ammonium formate (D), with a flow rate of 0.2 mL·min-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI+), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL-1, 3-100 ng·mL-1 and 0.9-30 ng·mL-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Rapid identification of chemical constituents in Xuezhikang Capsule by UPLC-Q-TOF/MSE combined with the establishment of UNIFI MS database / 药学学报

An UPLC-Q-TOF/MSE technology coupled with UNIFI database was used to develop a rapid, high coverage, accurate and efficient chemical composition qualitative method for Xuezhikang Capsule. A UNIFI database was established utilizing compound name, formula, structure, following automatic matching with high-resolution mass numbers, isotope distributions, mass deviations, fragment ion matching, and chromatographic retention features in UNIFI database to achieve the qualitative results of natural products in Xuezhikang Capsules. Combined with manual confirmation, 82 chemical components were identified in Xuezhikang Capsules, and the MS2 fragmentation pathway of typical organic acids, flavonoids, monacrines, and monascus were analyzed to ensure accuracy of the LC-MS workflow. This study clarified the chemical substance basis of Xuezhikang Capsules by LC-MS technology, providing experimental data support for the identification of key quality attributes, quality control and consistency evaluation in the manufacturing process of Xuezhikang Capsules.

Application of capillary zone electrophoresis to determine second-generation H1 antihistaminic drugs, loratadine and rupatadine

Abstract The second generation of H1 antihistamines from the piperidine group are often used for treating allergic diseases due to their action on histaminic receptors, the primary mediator of allergy. Moreover, the antihistamines have anti-inflammatory action, mediated through platelet-activating factor blocking activity. A simple and rapid capillary zone electrophoresis method was developed and validated for the determination of loratadine (LOR) and rupatadine (RUP) in tablets. The analyses were carried out using a fused silica capillary of 50.2 cm (40 cm effective length), 75 µm i.d. The background electrolyte was composed of boric acid 35 mmol/L, pH 2.5. Voltage of 20 kV, hydrodynamic injection of 3447.3 Pa for 3s, temperature at 25 ºC, and UV detection at 205 nm were applied. Electrophoretic separation was achieved at 1.8 and 2.8 min for RUP and LOR, respectively. The method was linear for both drugs in a range of 50.0 to 400.0 µg/mL (r>0.99). The limits of detection and quantification were 46.37 and 140.52 µg/mL, for LOR and 29.60 and 89.69 µg/mL for RUP respectively. The precision was less than 5.0 % for both drugs. The average recovery was approximately 100 %. The proposed novel method can significantly contribute to the rapid detection of counterfeit products and in quality control of drug products containing antihistamines

Development and validation of an HPLC-UV method for analysis of methylphenidate hydrochloride and loxapine succinate in an activated carbon disposal system / 药物分析学报

Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration (FDA) recommends the proper disposal of unused prescribed medications to maintain safety and prevent environmental hazards. However, many of the current disposal techniques do not properly address safety. A drug disposal pouch containing granular activated carbon offers a unique disposal method to deactivate residual or expiredmedication in a convenient, effective, and safe manner. A robust and validated method for methylphenidate hydrochloride and loxapine succinate was developed using high-performance liquid chromatography (HPLC) and the deactivation efficiency of the disposal system was tested. Methylphenidate hydrochloride was analyzed on a C18 analytical column (250mm × 4.60mm, 100?) using acetonitrile-water (0.05％ (v/v) trifluoroacetic acid) as the mobile phase at a flow rate of 1.0mL/min with a run time of 15min and retention time of 7.8min. Loxapine succinate was separated on a C8100? (250 mm × 4.6 mm, 5 μm) column maintained at 25 °C using a flow rate of 1.0mL/min. The run time was 10min and the retention time of the drug was around 4.6min.Mobile phase was composed of acetonitrile and water (0.3％ triethylamine) at pH 3.0 as 40:60 (v/v). Reference standard solutions (100 μg/mL) for both drugs were prepared by dissolving in mobile phases. These methods provide good linearity (R2 = 0.999) over the range of 5–100 μg/mL for methylphenidate hydrochloride and 0.1–100 μg/mL for loxapine succinate. The assay methods were successfully applied to study the deactivation of these drugs.

Development and validation of an HPLC method for the determination of epicatechin in Maytenus ilicifolia (Schrad.) Planch., Celastraceae / Desenvolvimento e validação de um método de CLAE para a determinação da epicatequina em Maytenus ilicifolia (Schrad.) Planch., Celastraceae

A simple, reproducible and efficient high-performance liquid chromatography (HPLC) method was developed. Water (0.05 percent TFA):acetonitrile (0.05 percent TFA) was used as the mobile phase in a gradient system for the determination of epicatechin (EP) in leaves of Maytenus ilicifolia (Schrad.) Planch. The analysis was performed using an RP C-18 column (5 µm) as the stationary phase, with a flow rate of 0.8 mL/min, at a wavelength of 210 nm for detection and determination. The main validation parameters of the method were also determined. The calibration curve was found to be linear, with a range of 10-120 µg/mL (EP). The correlation coefficient of the linear regression analysis was within 0.9988, and the detection and quantification limits were 28.61 and 86.77 µg/mL, respectively. The content of EP was successfully determined, with satisfactory reproducibility and recovery. Recovery of the EP was 99.32 percent. The method was successfully applied to the determination of epicatechin in leaves of M. ilicifolia. The interlaboratorial evaluation showed the reproducibility of the method with a relative standard deviation of 14.62 percent.

Um método simples, reprodutível e eficiente de cromatografia líquida de alta eficiência (CLAE) foi desenvolvido. Água (0,05 por cento TFA):acetonitrila (0,05 por cento TFA) foi utilizado como fase móvel em um sistema de gradiente para a determinação da epicatequina (EP) em folhas de Maytenus ilicifolia (Schrad.) Planch., Celastraceae. A análise foi realizada utilizando coluna RP C-18 (5 µm) como fase estacionária, com vazão de 0,8 mL/min, e comprimento de onda de 210 nm para a detecção e determinação. Os principais parâmetros de validação do método foram determinados. A curva analítica apresentou-se linear no intervalo de 10-120 µg/mL (EP). O coeficiente de correlação da análise de regressão linear foi de 0,9988, o limite de detecção e o limite de quantificação foram de 28,61 e 86,77 µg/mL, respectivamente. O conteúdo do EP foi determinado com sucesso, com boa reprodutibilidade e recuperação. Recuperação da EP foi 99,32 por cento. O método foi aplicado com sucesso na determinação da epicatequina em folhas de M. ilicifolia. A avaliação interlaboratorial demonstrou a reprodutibilidade do método com desvio padrão relativo de 14,62 por cento.