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1

LC-MS/MS method assay for simultaneous determination of the pretomanid and pyrazinamide in rat plasma by LC-MS/MS: Assessment of pharmacokinetic drug-drug interaction study

Huang Tao, Wang Li, Wang Fang, Shen Xin, Wang Libin

Acta Chromatographica

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2024

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Vol. 36, no. 1

7--13

EN

In the present study, an LC-MS/MS method allowing to quantify pretomanid and pyrazinamide simultaneously in rat plasma was developed. Chromatographic separation was achieved on an Agilent Eclipse plus C18 column (100 mm × 2.1 mm, 3.5 μm; Agilent, USA) and maintained at 30 °C. Multiple reaction monitoring (MRM) using positive-ion ESI mode to monitor ion transitions of m/z 360.1 → m/z 175.1 for pretomanid, m/z 124.1 → m/z 81.0 for pyrazinamide, m/z 172.1 → m/z 128.1 for metronidazole (IS). The calibration curves showed good linear relationships over the concentration range of 50–7,500 ng mL⁻¹ for pretomanid and 500–75,000 ng mL⁻¹ for pyrazinamide. The precision and accuracy were below 15% and within ±15% of the nominal concentrations, respectively. The selectivity, recovery and matrix effect of this method were all within acceptable limits of bioanalytics. The method was applied to the analysis of plasma samples from pharmacokinetic studies in rats. The results show that the main pharmacokinetic parameters of pyrazinamide, namely, T max , t1/2, and AUC(0–t), decreased in the combined group than in the alone group.

2

A simple, rapid, sensitive and eco-friendly LC-MS/MS method for simultaneous determination of free cordycepin and isocordycepin in 10 different kinds of Cordyceps

Li Wenqing, Qian Zhengming, Zou Yuansheng, Tan Guoying, Li Wenjia, Lei Qinggui, Li Runfeng, Lan Dongming

Acta Chromatographica

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2024

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Vol. 36, no. 1

59--66

EN

A simple, rapid, sensitive and eco-friendly liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of free cordycepin (3′-deoxyadenosine) and isocordycepin (2′-deoxyadenosine) in 10 kinds of Cordyceps samples. The samples were prepared by ultrasonic extraction at 75 °C for 30 min with boiling water as the extraction solvent. The LC separation was performed on an Agilent poroshell 120 SB-Aq C18 column (3.0 × 50 mm, 2.7 μm) in isocratic mode with an eco-friendly mobile phase (2% ethanol containing 0.2% acetic acid) at a flow rate of 0.6 mL min⁻¹, and detected by MS/MS in positive mode with multiple reaction monitoring (MRM). The developed method showed good linearity (r > 0.9990), sensitivity (LODs = 0.04 pg, LOQ = 0.1 pg), precision (RSD ≤ 3.8%) and stability (RSD ≤ 3.6%). The recoveries of developed method were 94.4–109.5% (RSD ≤ 5.5%). Compared with reported methods, the current method was rapid (less than 35% analytical time), sensitive (more than 5 folds), and eco-friendly (less than 10 μL harmful organic solvent). 10 different kinds of Cordyceps samples (40 batches) were tested by the developed method. Codycepin was only found in Cordyceps millitaris and C. millitaris fruiting body, and isocordycepin was detected in Cordyceps sinensis and other 6 Cordyceps samples. The developed method would be an improved method for the quality evaluation of Cordyceps samples.

3

Application of the QuEChERS Method for the Analysis of Contamination by Pesticide Residues in the Sediments of Three Moroccan Lagoons

Fegrouche Rachida, Dahak Hicham, El Kamli Taha, Oussekour Mohammed, Zaza Saida, Ben Salem Abdelkrim, Benyacoub Badreddine

Journal of Ecological Engineering

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2023

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Vol. 24, nr 12

336--345

EN

Agricultural, industrial, and domestic activities are major contributors to the contamination of natural environments. The aim of this study is to assess the level of sediment contamination by organic pollutants in three Moroccan lagoons: Moulay Bousselham, Oualidia, and Khnifiss. samples were analyzed using liquid chromatography (LC) coupled with mass spectrometry (MS) in Multiple Reaction Monitoring (MRM) mode to detect organophosphorus, carbamate, urea and its derivatives, and other chemical groups. Gas chromatography (GC) coupled with mass spectrometry (MS) was also used to analyze organochlorines. The samples were subjected to dispersive solid-phase extraction (dSPE) using QuEChERS before analysis. Fifteen active substances were detected, including organochlorines, organophosphates, carbamates, ureas, pyrethroids, and others. Three active substances, known for their high toxicity in aquatic environments (carbendazim, malathion, and chlorpyrifos), were identified. The heptachlor molecule (organochlorine family), although banned in Morocco, was still detected in the sediments of the lagoons of Oualidia and Khenifiss. Given the potential harm that these pesticides can cause to living organisms, it is crucial to introduce new crop protection techniques to address this issue.

4

Validated LC-MS/MS method for quantitation of solasodine in rat urine and feces: Blocking nonspecific adsorption

Lu Tiantian, Wang Xiaohong, Zhang Qi, Liu Kun, Xu Tongxin, Wang Quande, Zhao Pengfei, Cheng Zhongzhe

Acta Chromatographica

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2023

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Vol. 35, no. 4

319--325

EN

Solasodine, a steroidal alkaloid, is distributed extensively in Solanaceae plants with multiple biological activities such as neuroprotection, antineoplastic and anticonvulsant activities. However, there is little information about the excretion of intact solasodine in vivo. To investigate its excretion, a reliable LC-MS/MS method for quantitation solasodine in rat urine and feces was established and validated. Sample preparation was carried out by liquid-liquid extraction using MTBE as extractant. Moreover, rat urine was preconditioned with BSA, an anti-adsorptive additive, to prevent the nonspecific binding of solasodine to containers and tubes. The method was validated over the range of 4–2000 ng mL⁻¹. The correlation coefficient (r2t) were all above 0.999. The intra- and inter-day precision and accuracy were within 16.9% and between −11.0 and 8.9%, respectively. The recovery of solasodine in urine and feces was in the range of 72.5–80.3 and 75.7–80.2%, respectively. IS-normalized matrix factor ranged from 0.94 to 1.12 with RSD% ≤4.02%. This method was successfully applied to the excretion study of solasodine following oral and intravenous administration.

5

Simultaneous determination of eight antiepileptic drugs and two metabolites in human plasma by liquid chromatography/tandem mass spectrometry

Yu Hengyi, Ren Xiuhua, Liu Lu, Xiang Dong, Li Xiping, Li Juan, Liu Dong, Gong Xuepeng

Acta Chromatographica

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2023

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Vol. 35, no. 2

161--169

EN

Epilepsy is one of the most prevalent neurological conditions and antiepileptic drugs are the mainstay of epilepsy treatment. High variation in pharmacokinetic profiles of several antiepileptic drugs highlights the importance of therapeutic drug monitoring to estimate pharmacokinetic properties and consequently individualize drug posology. In this work, a simple, rapid and robust liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of carbamazepine and its metabolite carbamazepine-10,11-epoxide, gabapentin, levetiracetam, lamotrigine, oxcarbazepine and its metabolite mono-hydroxy-derivative metabolite, phenytoin, topiramate, and valproic acid in human plasma for therapeutic drug monitoring. d6-Levetiracetam, d4-gabapentin and d6-valproic acid were used as internal standards. After addition of internal standards along with two-step protein precipitation and dilution sample preparation, plasma samples were analyzed on a C18 column using a gradient elution in 5 min without interference. The calibration curves were linear over a 100-fold concentration range, with determination coefficients (r2) greater than 0.99 for all analytes. The limit of quantification was 0.5 μg mL⁻¹ (0.1 μg mL⁻¹ for oxcarbazepine, 2 μg mL⁻¹ for levetiracetam, and 10 μg mL⁻¹ for valproic acid) with precision and accuracy ranging from 3% to 9% and from 94% to 112%, respectively. Intra- and inter-day precision and accuracy values were within 15% at low, medium and high quality control levels. No significant matrix effect was observed in the normal, hemolyzed, lipemic, and hyperbilirubin blood samples. This method was successfully used in the identification and quantitation of antiepileptic drugs in patients undergoing mono- or polytherapy for epilepsy.

6

LC-MS/MS assay for the therapeutic drug monitoring of perampanel in children with drug-resistant epilepsy

Dai Hao-Ran, Hu Ya-Hui, Long Jia-Yi, Xia Ying, Guo Hong-Li, Xu Jing, Ding Xuan-Sheng, Chen Jing, Lu Xiao-Peng, Chen Feng

Acta Chromatographica

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2023

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Vol. 35, no. 2

149--160

EN

Perampanel (PER) is the first clinically available selective antagonist of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor approved globally for the treatment of epilepsy. Studies have recently underlined the significant association between dose-exposure-effect-adverse events of PER in patients with epilepsy, so the therapeutic drug monitoring (TDM) of PER is critical in clinical practices, especially for pediatric patients with drug-resistant epilepsy. Due to several limits in previous published analytical methods, herein, we describe the development and validation of a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for monitoring PER in human plasma samples. Protein precipitation method by acetonitrile containing PER-d5 as internal standard was applied for the sample clean-up. Formic acid (FA, 0.2 mM) in both aqueous water and acetonitrile were used as the mobile phases and the analyte was separated by an isocratic elution. Qualification and quantification were performed under positive electrospray ionization (ESI) mode using the m/z 350.3 → 219.1 and 355.3 → 220.0 ions pairs transitions for PER and PER-d5, respectively. Potential co-medicated anti-seizure medications (ASMs) have no interference to the analysis. Calibration curves were linear in the concentration range of 1.00–2,000 ng mL⁻¹ for PER. The intra- and inter-batch precision, accuracy, recovery, dilution integrity, and stability of the method were all within the acceptable criteria and no matrix effect or carryover was found. This method was then successfully implemented on the TDM of PER in Chinese children with drug-resistant epilepsy. We firstly confirmed the apparent inter- and intra-individual PER concentration variabilities and potential drug-drug interactions between PER and several concomitant ASMs occurred in Chinese pediatric patients, which were also in line with previous studies in patients of other race.

7

Simultaneous determination of rivaroxaban and sitagliptin in rat plasma by LC–MS/MS and its application to pharmacokinetic drug-drug interaction study

Wang Libin, Shang Kun, Zhang Xiaorui, Zhang Xinying, Feng Tian, Xu Xiaohui, Wang Fang

Acta Chromatographica

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2022

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Vol. 34, no. 4

430--436

EN

A sensitive and accurate LC-MS/MS method was developed and validated for the simultaneous quantification of rivaroxaban (RIV) and sitagliptin (SIT) in rat plasma using apixaban as internal standard (IS). An Agilent Eclipse plus C18 column (2.1 × 100 mm, 3.5 µm, Agilent) was used for chromatographic separation with isocratic elution. Multiple reaction monitoring (MRM) using positive-ion ESI mode to monitor ion transitions of m/z 436.8→144.9 for RIV, m/z 407.7→173.8 for SIT, m/z 459.8→442.8 for IS. The procedure of method validation included selectivity, linearity, precision, accuracy, matrix effect, extraction recovery and stability were conducted according to the guidelines of EMA and FDA. The results indicated that no obvious drug-drug interactions occurred might be owing to their differences in metabolic pathways.

8

Development of a rapid LC-MS/MS assay to determine letrozole in human plasma and its application in a pharmacokinetic study after oral administration

Li Pengfei, Zhang Xi, Wang Shumin, Wang Jing, Liu Ziqi, Wang Chen, Tong Weihang, Liu Lihong

Acta Chromatographica

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2022

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Vol. 34, no. 2

179--184

EN

Letrozole is one of the third generation aromatase inhibitors. It is suitable for the treatment of postmenopausal patients with advanced breast cancer and early treatment of breast cancer. It is necessary to develop a rapid, reliable, selective and sensitive LC–MS/MS assay to determine letrozole in human plasma to evaluate the clinical efficacy and adverse reactions with clinical pharmacokinetic and therapeutic drug monitoring. Separation was carried out on a Kromasil-C18 column using acetonitrile-water (55: 45, v/v) as mobile phase. Detection was carried out by multiple reaction monitoring on a 3200Qtrap mass spectrometry. The method needed one-step protein precipitation procedure only, and the cycle time was 2.5 min allowing 500–550 samples per day. It was linear within 0.30–50.00 ng/mL for plasma with the limit of detection (LOD) of 0.030 ng/mL. The intra- and inter-day RSD were 5.51–8.63%, 2.28–9.95% and the RE was 0.18–1.65%. The recovery rates of letrozole and internal standard for plasma were 89.30–98.55%. Letrozole was stable under all the conditions in the study. The method was sensitive enough to quantitate letrozole over a period of 288 h after giving a single oral dose of 2.5 mg–24 Chinese healthy volunteers. The absorption of letrozole was rapid with small individual difference, the tissue distribution of letrozole was more than that in blood, and the clearance was slow. Letrozole was similar to three-compartment model in vivo. Due to metabolism and excretion, the AUCs of letrozole varied greatly among individuals.

9

Development and validation of LC-MS/MS method for determination of plasma apixaban

Dzudovic Jelena, Crevar Sakac Milkica, Antunovic Marko, Repic Aleksandra, Obradovic Slobodan, Djordjevic Snezana, Savic Jelena, Dzudovic Boris

Acta Chromatographica

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2022

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Vol. 34, no. 3

332--337

EN

Oral anticoagulants are a group of drugs used for the prevention and treatment of venous thrombosis and venous thromboembolism. For the last ten years, direct oral anticoagulants (DOAC) have been available and are equally effective, but significantly safer than vitamin K antagonists. In the case of an overdose, their most important side effect is still bleeding. Due to their widespread use, as well as increased toxicological importance there is a need to develop an analytical method for the determination of DOAC in biological material. The aim of this paper was to establish a method for the quantification of apixaban as one of the representatives of DOAC. The methodology of the study included the measurement of apixaban in the plasma of patients treated in the intensive care unit. Plasma apixaban concentrations were determined by LC-MS/MS technique using carbamazepine as an internal standard. Obtained validation parameters indicate that the introduced method is sensitive, reliable, precise and accurate. Using this method, apixaban can be quickly and easily detected and quantified in plasma in patients who are suspected of overdosing with this drug.

10

Simultaneous quantification of cortisol and cortisone in serums and saliva from depressive patients by supported liquid extraction coupled to HPLC–MS/MSs

Chen Binbin, Lyu Haiyan, Xu Xiangzhen, Wang Chen

Acta Chromatographica

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2020

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Vol. 32, no. 4

269--275

EN

Cortisol and cortisone are 2 important glucocorticoids produced in the human hypothalamus–pituitary–adrenal (HPA) axis that respond to stress. An analytical method to determinate cortisol and cortisone in serum and saliva using high-performance liquid chromatography–tandem mass spectrometry following a supported liquid extraction (SLE) was developed. Serum and saliva samples of 0.2 mL were extracted by SLE three times using 0.4 mL of methyl tert-butyl ether each time. The chromatographic separation was obtained on an Agilent Poroshell column using a 0.01% formic acid buffer and acetonitrile (60:40, v/v) as the solvent with a flow rate of 0.3 mL/min. Optimized quantitative mass transitions for cortisol, cortisone, and cortisone d-4 were 363.2/121.0 (m/z), 361.2/163.1 (m/z), and 367.1/270.7 (m/z), respectively. The method validation was achieved according to regulatory guidance. The lower limit of quantification (LLOQ) in serum were 2 ng/mL for cortisol and 1 ng/mL for cortisone, and the LLOQ in saliva were 0.1 ng/mL for cortisol and 0.2 ng/mL for cortisone. The developed method showed convenient and efficient extraction, a lower LLOQ, and a short running time. Modest correlations between serum and saliva cortisol and cortisone concentrations were found. The method was successfully applied in assessing the HPA condition of patients with depressive disorders.

11

Determination of antibiotic residues in southern Baltic Sea sediments using tandem solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry

Siedlewicz G., Borecka M., Białk-Bielińska A., Sikora K., Stepnowski P., Pazdro K.

Oceanologia

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2016

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No. 58 (3)

221--234

EN

The main objective of this study was to adapt analytical procedures for determining antibiotic residues in solid and aquatic samples to marine sediments and to investigate the occurrence of 9 sulfonamides, trimethoprim and 2 quinolones in southern Baltic Sea sediments. The analytical procedure was applied to sediment samples characterized as sand and silty sand. The validation results showed that a sensitive and efficient method applying tandem solid-phase extraction (SPE) and liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) was obtained. Analytes were determined in the lower ng g−1 range with good accuracy and precision. The proposed analytical procedure was applied to the analysis of 13 sediment samples collected from the Baltic Sea along the Polish coast. Concentrations of antibiotic residues in environmental samples were calculated based on external matrix-matched calibration. Residues of nine out of twelve of the above antibiotics were detected in sediment samples in a concentrations of up to 419.2 ng g−1 d.w. (dry weight). Sulfamethoxazole and sulfachloropyridazine were the most frequently detected compounds (58% of the analyzed samples). The occurrence frequency of trimethoprim was 42% and it was always detected simultaneously with sulfamethoxazole. Preliminary studies on the spatial distribution of the analyzed antibiotics indicate a high level of antibiotics occurring in the Pomeranian Bay and close to the mouths of Polish rivers. The study is the first one to demonstrate the occurrence of antibiotic residues in sediments of the Polish coastal area. The obtained results suggest that sediment can be an important secondary source of antibiotic residues in the marine environment.

12

New Rapid Analysis of two Classes of Pesticides in Food Wastewater by Quechers-Liquid Chromatography/Mass Spectrometry

Łozowicka B., Kaczyński P., Szabuńko J., Ignatowicz K., Warentowicz D., Łozowicki J.

Journal of Ecological Engineering

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2016

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Vol. 17, nr 3

97--105

EN

The rapid analytical method was developed in response to increasing concern over the environmental impact of azoles (sterol biosynthesis inhibitors) and neonicotinoids (nicotinic acetylcholine receptor site). These chemicals are commonly used to protect fruit and vegetables crops against fungi and pests. Seven insecticides and twenty one fungicides commonly occurring in food industrial wastewater have been determined. For this purpose, active substances from two new pesticide classes were extracted and isolated by QuEChERS by addition of acetonitrile, buffering salts and chitin as a clean-up sorbent. The novelty of this procedure was one step sample preparation including extraction and removing of co-extracts in short time. Instrumental analysis was conducted by liquid chromatography coupled with mass spectrometry using multiple reaction monitoring. The limits of detection ranged from 0.002 to 0.005 μg·L-1 with satisfactory accuracy and precision The recoveries for the pesticides ranged from 81–103%, with high repeatability (n = 3, RSD ≤ 9%) and low LOQs (0.01 μg·L-1). Matrix effects calculated were less than 12% for all analyses. The method was applied to routine analysis of food industrial wastewater. Concerning the results, total pesticide levels in most cases were below 1 μg·L -1. The most significant pesticides in terms of concentration and frequency of detection were acetamiprid (0.07 μg· L-1); tebuconazole (1.2 μg· L-1) and thiacloprid (0.04 μg·L-1).

13

LC—MS/MS method for quantification of atorvastatin, o-hydroxyatorvastatin, p-hydroxyatorvastatin, and atorvastatin lactone in rat plasma

Crevar-Sakač M., Vujić Z., Vujčić Z., Marković B., Vasiljević D.

Acta Chromatographica

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2016

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Vol. 28, no. 3

281--298

EN

A simple and sensitive liquid chromatography—tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C18 Analytical, 4.6 × 100 mm (3.5 μm) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 μL min−1. The column was kept at constant temperature (25 °C), and autosampler tray temperature was set at 4 °C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 → Q3, collision energy) atorvastatin (559.47 → 440.03, 22 eV), atorvastatin lactone (541.36 → 448.02, 19 eV), ortho-ohydroxyatorvastatin (575.20 → 440.18, 20 eV), para-hydroxyatorvastatin (575.54 → 440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5–20 ng mL−1 for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1–20 ng mL−1 for atorvastatin and atorvastatin lactone with excellent linearity (r2 ≥ 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL−1 for orth-ohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL−1 for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.

14

Development and Validation of an LC–MS/MS Method for Determination of Tigecycline and Its Epimer in Human Plasma and Its Application in a Pharmacokinetic Study

Wang L., Hu X., Zhu H., Zhang X., Wang C., Han Z.

Acta Chromatographica

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2016

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Vol. 28, no. 2

239--253

EN

A rapid, selective, sensitive, and simple method for simultaneous determination of tigecycline and its epimer in human plasma samples was developed and validated by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Sample preparation involved one-step protein precipitation by adding 0.1% formic acid–methanol and phosphate buffer (PB) solution to the plasma. Chromatographic separation was obtained with XBridge BEH C18 column (3.5 μm, 50 × 4.6 mm) through a 9.5-min gradient mobile phase at the flow rate of 0.6 mL min−1 at 4 °C. The calibration curves were linear over concentration 5.00–2000 ng mL−1 with correlation coefficient greater than 0.998. Intra-batch and inter-batch accuracy of the assay were in the ranges of −2.90% to 3.00%, and the corresponding precision was less than 6.97%. The extraction recovery of tigecycline and its epimer with the current method were 87.2% and 76.9%, respectively. The applied LC–MS/MS method was shown to be sufficiently sensitive and will be suitable for pharmacokinetic studies.

15

Development and validation of a sensitive and selective LC—MS/MS method for the determination of an antimalarial drug candidate in rat plasma, and its application to a preclinical pharmacokinetic study

Pires C., Kaiser M., Grünspan L. D., Barreto F., Innocente A., Gnoatto S., Laureano J. V., Araujo B., Costa T., Tasso L.

Acta Chromatographica

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2016

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Vol. 28, no. 4

439--453

EN

An accurate and reliable LC—MS/MS assay was firstly developed and validated for quantitative determination of a new antimalarial prototype drug, 3β-hydroxyurs-12-en-28-oic acid (LAFIS 01), in rat plasma. Dexamethasone was employed as internal standard. Simple protein precipitation by acetonitrile for the sample preparation was used. Effective separation was achieved with Phenomenex Luna C18 (50 × 2 mm, 5 μm) column. The mobile phase consisted of (A) water and (B) acetonitrile, both containing 0.1% acetic acid, delivered by gradient elution. The column temperature was maintained at 40 °C. The LAFIS 01 was monitored by electrospray ionization interface, operating in the negative mode (ESI−) in multiple reactions monitoring (MRM), checking the transitions 455 > 455 for LAFIS 01 and 451 > 361 for the IS. Once LAFIS 01 demonstrated low fragmentation by collision-induced dissociation (CID) nonpresenting abundant high-intensity fragments to meet the desired concentration levels quantification, only pseudomolecular ion was monitored. The flow rate was 500 μL min−1. The lower limit of quantitation achieved was 10 ng mL−1 and linearity was observed from 10 to 500 ng mL−1. The relative standard deviation (RSD) values of the intra- and inter-assay precisions of the method were below 8.42 and 7.94%, respectively. The accuracy ranged from 92.05 to 102.94%. The extraction recovery of LAFIS 01 and IS was up to 90%. The method showed linearity, precision, accuracy, sensitivity, and stability required to quantify LAFIS 01 in preclinical pharmacokinetic study.

16

Liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of Vildagliptin in rat plasma

Sakthimanigandan K., Ganesh M., Kanthikiran V., Sivakumar T., Jang H.

Acta Chromatographica

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2015

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Vol. 27, no. 2

295--307

EN

A new sensitive and validated liquid chromatography electro spray ion-tandem mass spectrometry (HPLC-ESI-MS/MS) method for the quantification of Vildagliptin (VG) in rat plasma has been developed and validated using repaglinide (RG) as an internal standard (IS). The analytes were extracted by liquid-liquid extraction using ethyl acetate. Elution of the VG and IS was achieved on a reverse phase Betasil (C18 50 mm 4.6 mm ID, 5 μ) column with an isocratic mobile phase composed of acetonitrile: 2 mM ammonium acetate (90:10 v/v). The analytes monitored in the Multiple Reaction Monitoring (MRM) mode were m/z 304.2→154.0 and 453.3→230.3 for VG and RG, respectively. The calibration curve was linear in the range of 1.57–501.21 ng/mL for VG with lower limit of quantification 1.57 ng/mL. The intra run and inter run precision values are within 11.70% for VG at LOQ level.

17

A validated liquid chromatography and tandem mass spectrometric method for simultaneous quantitation of tenofovir, emtricitabine, and efavirenz in human plasma and its pharmacokinetic application

Matta M. K, Pilli N. R, Rao J.V.L.N. S.

Acta Chromatographica

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2015

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Vol. 27, no. 1

27--39

EN

A novel, rapid, and sensitive liquid chromatography-tandem mass spectrometric method was developed and validated for the simultaneous quantification of tenofovir, emtricitabine, and efavirenz in human plasma. Nevirapine was used as an internal standard. The analytes and the internal standard were extracted from human plasma sample by solid-phase extraction technique (SPE). The reconstituted samples were chromatographed on a Chromolith ROD C18 column (50 × 4.6 mm; 5 μ) by gradient elution using a mixture of ammonium acetate buffer (5 mM) and 0.1% formic acid in acetonitrile as the mobile phase at a flow rate of 1.0 mL min -1. The calibration curve obtained was linear (r2 ≥ 0.9990) over the concentration range of 2.5–650 ng mL -1 for tenofovir and 10–4000 ng mL -1 for emtricitabine and efavirenz. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies, and the authenticity in the measurement of clinical data is demonstrated through incurred samples reanalysis (ISR).

18

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSn and 2D-NMR

Thomas S., Paul S. K., Agarwal A., Mathela C. S.

Acta Chromatographica

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2014

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Vol. 26, no. 3

429--438

EN

Galantamine hydrobromide was subjected to oxidative stress degradation using hydrogen peroxide and analyzed as per the chromatographic conditions described in European Pharmacopoeia. The drug showed considerable degradation at ambient temperature resulting in the formation of two degradation products at relative retention times (RRTs) 0.63 and 2.52. The minor degradant at RRT 0.63 was identified as galantamine N-oxide. The principal degradant formed at RRT 2.52 was found to be unknown and has not been reported previously. The unknown impurity was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by isolation using semi-preparative high-performance liquid chromatography (HPLC). The isolated impurity was characterized using one-dimensional, two-dimensional nuclear magnetic resonance spectroscopy (1D and 2D NMR) and elemental analysis (EA). The principal degradant was found to be formed due to the generation of bromine and subsequent attack on the aromatic ring via in situ reaction between hydrogen bromide and hydrogen peroxide. The unknown impurity was characterized as (4aS,6R,8aS)-5,6,9,10,11,12-hexahydro-1-bromo-3-methoxy-11-methyl-4aH-[1]benzofuro [3a,3,2-ef] [2] benzazepin-6-ol.

19

Identification and simultaneous determination of glycyrrhizin, formononetin, glycyrrhetinic acid, liquiritin, isoliquiritigenin, and licochalcone A in licorice by LC-MS/MS

Xie J., Zhang Y., Wang W., Hou J.

Acta Chromatographica

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2014

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Vol. 26, no. 3

507--516

EN

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of glycyrrhizin, formononetin, glycyrrhetinic acid, liquiritin, isoliquiritigenin, and licochalcone A in licorice. An Eclipse Plus C18 column (I.D. 4.6 × 100 mm, 3.5 μm particle size; Agilent) was used in the analysis. Electrospray ionization (ESI)-tandem interface in the negative mode was performed, and multiple reaction monitoring (MRM) was employed with the precursor multiple reaction monitoring production combination for the determination of six analytes. The average recoveries ranged from 98.30% to 100.13% with relative standard deviations (RSDs) ≤ 1.95%, and limits of detection (LODs) ranged from 2.1 to 3.6 pg. The applicability of this analytical approach was confirmed by the successful analysis of six samples. The results indicated that the established method was validated, sensitive, and reliable for the determination of six analytes in licorice.

20

Development and validation of a rapid and sensitive LC-MS/MS method for the determination of aripiprazole in human plasma: Application to a bioequivalence study

Patel D. S., Sharma N., Patel M. C., Patel B. N., Shrivastav P. S., Sanyal M.

Acta Chromatographica

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2014

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Vol. 26, no. 2

203--227

EN

A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of aripiprazole in human plasma. The analyte and propranolol as internal standard (IS) were extracted from 200 μL of human plasma via liquid-liquid extraction using methyl tert-butyl ether under alkaline conditions. The best chromatographic separation was achieved on an Aquasil C18 (100 × 2.1 mm, 5 μm) column using methanol-deionized water containing 2 mM ammonium trifluoroacetate and 0.02% formic acid (65:35, v/v) as the mobile phase under isocratic conditions. Detection of analyte and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The method was fully validated for its selectivity, interference check, sensitivity, carryover check, linearity, precision and accuracy, reinjection reproducibility, recovery, matrix effect, ion suppression/enhancement, stability, ruggedness, and dilution integrity. The assay was linear over the concentration range of 0.10–100 ng mL -1 for aripiprazole. The intra-batch and inter-batch precision (%CV) was ≤4.8%, while the mean extraction recovery was >96% for aripiprazole across quality control levels. The method was successfully applied to a bioequivalence study of 10 mg aripiprazole orally disintegrating tablet formulation in 27 healthy Indian subjects under fasting and fed condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 260 incurred samples.