Submit to Molecules Review for Molecules Propose a Special Issue

Journal Browser

► Journal Browser

Method Development and Validation in Food and Pharmaceutical Analysis III

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Analytical Chemistry".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 34257

Share This Special Issue

Special Issue Editors

Prof. Dr. In-Soo Yoon

E-Mail Website
Guest Editor

Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Geumjeong-gu, Busan 46241, Republic of Korea
Interests: bioanalysis; biopharmaceutics; DMPK; PBPK/PD modeling
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Hyun-Jong Cho

E-Mail Website
Guest Editor

College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
Interests: spectroscopy; imaging analysis; formulation; drug delivery system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Analytical chemistry is the study of separation, identification, and quantification of natural and artificial materials composed of one or more compounds or elements. The rapid growth of the food and pharmaceutical industries and the production of drugs and functional foods around the world have brought forward an inevitable rise in the demand to seek novel and systematic analytical techniques. As a consequence, analytical method development and validation have become a crucial prerequisite for achieving reliable analytical data required to support food and pharmaceutical development processes.

This Special Issue on “Method Development and Validation in Food and Pharmaceutical Analysis III” will cover a wide range of topics including, but not limited to, new analytical and bioanalytical methods relevant to the separation, identification, and determination of substances in pharmaceutics, pharmacokinetics, nanobiotechnology, clinical chemistry, biomedical engineering, and related disciplines.

We warmly invite our colleagues to submit their original contributions to this Special Issue in order to provide recent updates regarding analytical methods for drugs, biologics, phytochemicals, and other organic/inorganic materials related to food and pharmaceutical sciences that are appealing to readers. We would be delighted if you could respond to confirm your contribution and the proposed title by 31 March 2022.

Prof. Dr. In-Soo Yoon
Prof. Dr. Hyun-Jong Cho
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

HPLC
Bioanalysis
Phytochemicals
Pharmacokinetics
Mass spectrometry
Functional food
Biopharmaceutics
Natural and synthetic polymers
Inorganic materials
Pharmaceutical formulations
Imaging analysis
Spectroscopy

Published Papers (12 papers)

Download All Papers

Research

13 pages, 3383 KiB

Open AccessArticle

Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses

by Sihyun Jeong, Yuju Kim, Soyeong Park, Doyeon Lee, Juho Lee, Shwe Phyu Hlaing, Jin-Wook Yoo, Sang Hoon Rhee and Eunok Im

Molecules 2023, 28(4), 1890; https://doi.org/10.3390/molecules28041890 - 16 Feb 2023

Cited by 9 | Viewed by 2502

Abstract

Lactobacillus plantarum (L. plantarum) is a probiotic that has emerged as novel therapeutic agents for managing various diseases, such as cancer, atopic dermatitis, inflammatory bowel disease, and infections. In this study, we investigated the potential mechanisms underlying the anticancer effect of the metabolites of L. plantarum. We cultured L. plantarum cells to obtain their metabolites, created several dilutions, and used these solutions to treat human colonic Caco-2 cells. Our results showed a 10% dilution of L. plantarum metabolites decreased cell viability and reduced the expression of autophagy-related proteins. Moreover, we found co-treatment with L. plantarum metabolites and chloroquine, a known autophagy inhibitor, had a synergistic effect on cytotoxicity and downregulation of autophagy-related protein expression. In conclusion, we showed the metabolites from the probiotic, L. plantarum, work synergistically with chloroquine in killing Caco-2 cells and downregulating the expression of autophagy-related proteins, suggesting the involvement of autophagy, rather than apoptosis, in their cytotoxic effect. Hence, this study provides new insights into new therapeutic methods via inhibiting autophagy. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

11 pages, 1464 KiB

Open AccessArticle

Determination of Leuprolide–Fatty Acid Conjugate in Rat Plasma Using LC-MS/MS and Its Pharmacokinetics after Subcutaneous Administration in Rats

by Gi-Sang Seong, Seong-Wook Seo, Ji Young Cho, Kye Wan Lee, Beom-Jin Lee, In-Soo Yoon and Hyo-Eon Jin

Molecules 2022, 27(24), 8716; https://doi.org/10.3390/molecules27248716 - 9 Dec 2022

Cited by 2 | Viewed by 1659

Abstract

Leuprolide is a synthetic nonapeptide drug (pyroGlu-His-Trp-Ser-Tyr-d-Leu-Leu-Arg-Pro-NHEt) that acts as a gonadotropin-releasing hormone agonist. The continuous administration of therapeutic doses of leuprolide inhibits gonadotropin secretion, which is used in androgen-deprivation therapy for the treatment of advanced prostate cancer, central precocious puberty, endometriosis, uterine fibroids, and other sex-hormone-related conditions. To improve the pharmacokinetic properties of peptide drugs, a fatty acid was conjugated with leuprolide for long-term action. In this study, we developed a simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of leuprolide and leuprolide–oleic acid conjugate (LOC) levels. The developed method was validated in terms of linearity, precision, accuracy, recovery, matrix effect, and stability according to the US Food and Drug Administration guidelines, and the parameters were within acceptable limits. Subsequently, the pharmacokinetics of leuprolide and LOCs were evaluated. In vivo rat subcutaneous studies revealed that conjugation with fatty acids significantly altered the pharmacokinetics of leuprolide. After the subcutaneous administration of fatty-acid-conjugated leuprolide, the mean absorption time and half-life were prolonged. To the best of our knowledge, this is the first study showing the effects of fatty acid conjugates on the pharmacokinetics of leuprolide using a newly developed UPLC-MS/MS method for the simultaneous quantification of leuprolide and LOCs. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

13 pages, 1416 KiB

Open AccessArticle

Simultaneous Determination of Moxifloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Rabbit Ocular Tissues and Plasma by LC-MS/MS: Application for Pharmacokinetics Studies

by Xinxin Zhao, Yanjuan Yuan, Qing Shao and Hongqun Qiao

Molecules 2022, 27(22), 7934; https://doi.org/10.3390/molecules27227934 - 16 Nov 2022

Cited by 3 | Viewed by 1874

Abstract

Treatment of ocular infection involves pharmacotherapy with steroids and antibiotic drops, such as moxifloxacin hydrochloride (MFH) and dexamethasone sodium phosphate (DSP). To characterize the pharmacokinetics of these two compounds, we performed and validated a liquid chromatography-mass spectrometry (LC-MS/MS) method to quantify them in rabbit ocular tissues and plasma. We used protein precipitation to extract the compounds. The analyte and internal standard (IS) were separated using a Shim-pack Scepter C₁₈ column. The mobile phase was composed of 0.1% formic acid water (A) and methanol (B). MFH and DSP were detected using positive ion electrostatic ionization (ESI) in multiple reaction monitoring mode (MRM). The calibration curves for both compounds showed good linearity over concentrations ranging from 0.5 to 200 ng/mL in rabbit ocular tissues and plasma. The lower limit of quantification for both MFH and DSP was 0.5 ng/mL. We validated this method for selectivity, linearity (r2 > 0.99), precision, accuracy, matrix effects, and stability. Thus, we used this method to assess the pharmacokinetic (PK) characteristics of MFH and DSP in rabbit ocular tissues and plasma after single doses. Our results indicate that this method can be used for the simultaneous analysis of moxifloxacin hydrochloride and dexamethasone sodium phosphate in clinical samples. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

10 pages, 1084 KiB

Open AccessArticle

A Rapid and Sensitive LC−MS/MS Method for the Quantitation of Physalin A with Special Consideration to Chemical Stability in Rat Plasma: Application to a Pharmacokinetic Study

by Yang Li, Na Zhao, Tingting Zhang and Xinchi Feng

Molecules 2022, 27(21), 7272; https://doi.org/10.3390/molecules27217272 - 26 Oct 2022

Viewed by 1004

Abstract

Physalin A is a promising natural product with excellent anti-inflammatory and anti-tumor activities. However, the pharmacokinetic profile of physalin A is still unclear. In this study, a rapid and sensitive analytical method based on LC–MS/MS for the quantitation of physalin A in rat plasma with special consideration to its chemical stability was developed and validated. To avoid the degradation of physalin A, the separation of plasma was conducted at 4 °C directly after the blood samples were collected. Meanwhile, plasma samples were immediately precipitated with acetonitrile containing tolbutamide (internal standard, IS) and the pH of the supernatant was adjusted to 1.5 with formic acid. Chromatographic separation of physalin A and IS was achieved on an ACQUITY UPLC BEH-C18 column (2.1 × 50 mm, 1.7 μm) using 0.1% formic acid and acetonitrile as mobile phase delivered at 0.3 mL/min in a gradient elution mode. Physalin A and IS were detected through negative ion electrospray ionization in multiple reaction monitoring (MRM) mode. The MS/MS ion transitions for physalin A and IS were m/z 525.1–148.9 and m/z 269.8–169.9, respectively. The developed method showed good linearity over the range of 2.00–400 ng/mL. This method was successfully applied to the pharmacokinetic study of physalin A in rats following its intragastric administration and the findings were beneficial for future studies of physalin A. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Graphical abstract

16 pages, 2074 KiB

Open AccessArticle

Development of UPLC-MS/MS Method to Study the Pharmacokinetic Interaction between Sorafenib and Dapagliflozin in Rats

by Xueru He, Ying Li, Yinling Ma, Yuhao Fu, Xuejiao Xun, Yanjun Cui and Zhanjun Dong

Molecules 2022, 27(19), 6190; https://doi.org/10.3390/molecules27196190 - 21 Sep 2022

Cited by 5 | Viewed by 2412

Abstract

Sorafenib (SOR), an inhibitor of multiple kinases, is a classic targeted drug for advanced hepatocellular carcinoma (HCC) which often coexists with type 2 diabetes mellitus (T2DM). Dapagliflozin (DAPA), a sodium–glucose cotransporter-2 inhibitor (SGLT2i), is widely used in patients with T2DM. Notably, co-administration of SOR with DAPA is common in clinical settings. Uridine diphosphate-glucuronosyltransferase family 1 member A9 (UGT1A9) is involved in the metabolism of SOR and dapagliflozin (DAPA), and SOR is the inhibitor of UGT1A1 and UGT1A9 (in vitro). Therefore, changes in UGT1A9 activity caused by SOR may lead to pharmacokinetic interactions between the two drugs. The objective of the current study was to develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of SOR and DAPA in plasma and to evaluate the effect of the co-administration of SOR and DAPA on their individual pharmacokinetic properties and the mechanism involved. The rats were divided into four groups: SOR (100 mg/kg) alone and co-administered with DAPA (1 mg/kg) for seven days, and DAPA (1 mg/kg) alone and co-administered with SOR (100 mg/kg) for seven days. Liquid–liquid extraction (LLE) was performed for plasma sample preparation, and the chromatographic separation was conducted on Waters XSelect HSS T3 column with a gradient elution of 0.1% formic acid and 5 mM ammonium acetate (Phase A) and acetonitrile (Phase B). The levels of Ugt1a7 messenger RNA (mRNA) were determined in rat liver and intestine using quantitative real-time polymerase chain reaction (qRT-PCR). The method was successfully applied to the study of pharmacokinetic interactions. DAPA caused a significant decrease in the maximum plasma concentrations (Cmax) and the area under the plasma concentration–time curves (AUC_0–t) of SOR by 41.6% and 50.5%, respectively, while the apparent volume of distribution (V_z/F) and apparent clearance (CL_z/F) significantly increased 2.85- and 1.98-fold, respectively. When co-administering DAPA with SOR, the AUC_0–t and the elimination half-life (t_1/2Z) of DAPA significantly increased 1.66- and 1.80-fold, respectively, whereas the CL_z/F significantly decreased by 40%. Results from qRT-PCR showed that, compared with control, seven days of SOR pretreatment decreased Ugt1a7 expression in both liver and intestine tissue. In contrast, seven days of DAPA pretreatment decreased Ugt1a7 expression only in liver tissue. Therefore, pharmacokinetic interactions exist between long-term use of SOR with DAPA, and UGT1A9 may be the targets mediating the interaction. Active surveillance for the treatment outcomes and adverse reactions are required. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

15 pages, 2776 KiB

Open AccessArticle

Pharmacokinetic Interactions between Canagliflozin and Sorafenib or Lenvatinib in Rats

by Yanjun Cui, Ying Li, Caihui Guo, Yajing Li, Yinling Ma and Zhanjun Dong

Molecules 2022, 27(17), 5419; https://doi.org/10.3390/molecules27175419 - 24 Aug 2022

Cited by 3 | Viewed by 2160

Abstract

Hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM) are common clinical conditions, and T2DM is an independent risk factor for HCC. Sorafenib and lenvatinib, two multi-targeted tyrosine kinase inhibitors, are first-line therapies for advanced HCC, while canagliflozin, a sodium-glucose co-transporter 2 inhibitor, is widely used in the treatment of T2DM. Here, we developed an ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of canagliflozin, sorafenib, and lenvatinib, and investigated the pharmacokinetic drug interactions between canagliflozin and sorafenib or lenvatinib in rats. The animals were randomly divided into five groups. Groups I–III were gavage administrated with sorafenib, lenvatinib, and canagliflozin, respectively. Group IV received sorafenib and canagliflozin; while Group V received lenvatinib and canagliflozin. The area under the plasma concentration-time curves (AUC) and maximum plasma concentrations (C_max) of canagliflozin increased by 37.6% and 32.8%, respectively, while the apparent volume of distribution (V_z/F) and apparent clearance (CL_z/F) of canagliflozin significantly decreased (30.6% and 28.6%, respectively) in the presence of sorafenib. Canagliflozin caused a significant increase in AUC and C_max of lenvatinib by 28.9% and 36.2%, respectively, and a significant decrease in V_z/F and CL_z/F of lenvatinib by 52.9% and 22.7%, respectively. In conclusion, drug interactions exist between canagliflozin and sorafenib or lenvatinib, and these findings provide a reference for the use of these drugs in patients with HCC and T2DM. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

11 pages, 901 KiB

Open AccessArticle

Determination of Osimertinib, Aumolertinib, and Furmonertinib in Human Plasma for Therapeutic Drug Monitoring by UPLC-MS/MS

by Ying Li, Lu Meng, Yinling Ma, Yajing Li, Xiaoqing Xing, Caihui Guo and Zhanjun Dong

Molecules 2022, 27(14), 4474; https://doi.org/10.3390/molecules27144474 - 13 Jul 2022

Cited by 5 | Viewed by 2416

Abstract

The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib, aumolertinib, and furmonertinib represent a new treatment option for patients with EGFR p.Thr790 Met (T790 M)-mutated non-small cell lung cancer (NSCLC). Currently, there are no studies reporting the simultaneous quantification of these three drugs. A simple ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of osimertinib, aumolertinib, and furmonertinib concentrations in human plasma, and it was applied for therapeutic drug monitoring (TDM). Plasma samples were processed using the protein precipitation method (acetonitrile). A positive ion monitoring mode was used for detecting analytes. D₃-Sorafenib was utilized as the internal standard (IS), and the mobile phases were acetonitrile (containing 0.1% formic acid) and water with gradient elution on an XSelect HSS XP column (2.1 mm × 100.0 mm, 2.5 µm, Waters, Milford, MA, USA) at a flow rate of 0.5 mL·min⁻¹. The method’s selectivity, precision (coefficient of variation of intra-day and inter-day ≤ 6.1%), accuracy (95.8–105.2%), matrix effect (92.3–106.0%), extraction recovery, and stability results were acceptable according to the guidelines. The linear ranges were 5–500 ng·mL⁻¹, 2–500 ng·mL⁻¹, and 0.5–200 ng·mL⁻¹ for osimertinib, aumolertinib, and furmonertinib, respectively. The results show that the method was sensitive, reliable, and simple and that it could be successfully applied to simultaneously determine the osimertinib, aumolertinib, and furmonertinib blood concentrations in patients. These findings support using the method for TDM, potentially reducing the incidence of dosing blindness and adverse effects due to empirical dosing and inter-patient differences. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

10 pages, 989 KiB

Open AccessArticle

Development and Validation of a Method of Liquid Chromatography Coupled with Tandem Mass Spectrometry for Quantification of ST-246 (Tecovirimat) in Human Plasma

by Galina A. Oleinik, Vladimir V. Koval, Svetlana V. Usova, Larisa N. Shishkina and Alexander A. Chernonosov

Molecules 2022, 27(11), 3577; https://doi.org/10.3390/molecules27113577 - 2 Jun 2022

Cited by 6 | Viewed by 1463

Abstract

The aim of this work was to develop and validate a sensitive and robust method of liquid chromatography coupled with tandem mass spectrometry to quantitate ST-246 (tecovirimat) in plasma using an internal standard (2-hydroxy-N-{3,5-dioxo-4-azatetracyclo [5.3.2.02.6.08.10]dodec-11-en-4-yl}-5-methylbenzamide). The method was validated in negative multiple reaction monitoring mode following recommendations of the European Medicines Agency for the validation of bioanalytical methods. The calibration curve for the analyte was linear in the 10–2500 ng/mL range with determination coefficient R² > 0.99. Intra- and inter-day accuracy and precision for three concentrations of quality control were <15%. Testing of long-term stability of ST-246 (tecovirimat) in plasma showed no degradation at −20 °C for at least 3 months. The method was applied to a clinical assay of a new antipoxvirus compound, NIOCH-14. Thus, the proposed method is suitable for therapeutic drug monitoring of ST-246 (tecovirimat) itself and of NIOCH-14 as its metabolic precursor. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

15 pages, 1970 KiB

Open AccessArticle

Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies

by Thi-Thao-Linh Nguyen, Jin Woo Kim, Hae-In Choi, Han-Joo Maeng and Tae-Sung Koo

Molecules 2022, 27(6), 1977; https://doi.org/10.3390/molecules27061977 - 18 Mar 2022

Cited by 24 | Viewed by 6501

Abstract

ARV-110, a novel proteolysis-targeting chimera (PROTAC), has been reported to show satisfactory safety and tolerability for prostate cancer therapy in phase I clinical trials. However, there is a lack of bioanalytical assays for ARV-110 determination in biological samples. In this study, we developed and validated an LC-MS/MS method for the quantitation of ARV-110 in rat and mouse plasma and applied it to pharmacokinetic studies. ARV-110 and pomalidomide (internal standard) were extracted from the plasma samples using the protein precipitation method. Sample separation was performed using a C18 column and a mobile phase of 0.1% formic acid in distilled water–0.1% formic acid in acetonitrile (30:70, v/v). Multiple reaction monitoring was used to quantify ARV-110 and pomalidomide with ion transitions at m/z 813.4 → 452.2 and 273.8 → 201.0, respectively. The developed method showed good linearity in the concentration range of 2–3000 ng/mL with acceptable accuracy, precision, matrix effect, process efficiency, and recovery. ARV-110 was stable in rat and mouse plasma under long-term storage, three freeze-thaw cycles, and in an autosampler, but unstable at room temperature and 37 °C. Furthermore, the elimination of ARV-110 via phase 1 metabolism in rat, mouse, and human hepatic microsomes was shown to be unlikely. Application of the developed method to pharmacokinetic studies revealed that the oral bioavailability of ARV-110 in rats and mice was moderate (23.83% and 37.89%, respectively). These pharmacokinetic findings are beneficial for future preclinical and clinical studies of ARV-110 and/or other PROTACs. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

13 pages, 1807 KiB

Open AccessArticle

Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis

by Hyeon Seok Oh, Taehyung Kim, Dong-Hyeon Gu, Tae Suk Lee, Tae Hwan Kim, Soyoung Shin and Beom Soo Shin

Molecules 2022, 27(6), 1881; https://doi.org/10.3390/molecules27061881 - 14 Mar 2022

Cited by 4 | Viewed by 2455

Abstract

Nafamostat, a synthetic serine protease inhibitor, has been used for the treatment of inflammatory diseases such as pancreatitis. Recently, an increasing number of studies have shown the promising antiviral effects of nafamostat for the treatment of coronavirus disease-19 (COVID-19). This study aimed to develop a novel liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis and to characterize the pharmacokinetics of nafamostat in rats. Nafamostat in the rat plasma was extracted by solid phase extraction, and ¹³C₆-nafamostat was used as an internal standard. The quantification limit of nafamostat in the rat plasma was 0.5 ng/mL. The LC-MS/MS method was fully validated and applied to characterize the pharmacokinetics of nafamostat in rats. Following intravenous injection (2 mg/kg), nafamostat in the plasma showed a multiexponential decline with an average elimination half-life (t_1/2) of 1.39 h. Following oral administration of nafamostat solutions (20 mg/kg) in 10% dimethyl sulfoxide (DMSO) and in 10% DMSO with 10% Tween 80, nafamostat was rapidly absorbed, and the average oral bioavailability was 0.95% and 1.59%, respectively. The LC-MS/MS method and the pharmacokinetic information of nafamostat could be helpful for the further preclinical and clinical studies of nafamostat. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

12 pages, 1511 KiB

Open AccessArticle

A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study

by Yanjun Cui, Ying Li, Xiao Li, Liju Fan, Xueru He, Yuhao Fu and Zhanjun Dong

Molecules 2022, 27(4), 1291; https://doi.org/10.3390/molecules27041291 - 15 Feb 2022

Cited by 4 | Viewed by 2233

Abstract

Lenvatinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis, but hypertension is the most common adverse reaction. Telmisartan is an angiotensin receptor blocker used to treat hypertension. In this study, a simple ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of lenvatinib and telmisartan, and it was applied to the pharmacokinetic drug interaction study. Plasma samples were treated with acetonitrile to precipitate protein. Water (containing 5 mM of ammonium acetate and 0.1% formic acid) and acetonitrile (0.1% formic acid) were used as the mobile phases to separate the analytes with gradient elution using a column XSelect HSS T3 (2.1 mm × 100 mm, 2.5 μm). Multiple reaction monitoring in the positive ion mode was used for quantification. The method was validated and the precision, accuracy, matrix effect, recovery, and stability of this method were reasonable. The determination of analytes was not interfered with by other substances in the blank plasma, and the calibration curves of lenvatinib and telmisartan were linear within the range of 0.2–1000 ng/mL and 0.1–500 ng/mL, respectively. The results indicate that lenvatinib decreased the systemic exposure of telmisartan. Potential drug interactions were observed between lenvatinib and telmisartan. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

12 pages, 994 KiB

Open AccessArticle

Eco-Friendly, Simple, Fast, and Sensitive UPLC-MS/MS Method for Determination of Pexidartinib in Plasma and Its Application to Metabolic Stability

by Essam Ezzeldin, Muzaffar Iqbal, Yousif A. Asiri, Gamal A. E. Mostafa and Ahmed Y. A. Sayed

Molecules 2022, 27(1), 297; https://doi.org/10.3390/molecules27010297 - 4 Jan 2022

Cited by 2 | Viewed by 1762

Abstract

Pexidartinib is the first drug approved by the U.S. Food and Drug Administration specifically to treat the rare joint tumor tenosynovial giant cell tumor. In the current study, a validated, selective, and sensitive UPLC-MS/MS assay was developed for the quantitative determination of pexidartinib in plasma samples using gifitinib as an internal standard (IS). Pexidartinib and IS were extracted by liquid-liquid extraction using methyl tert-butyl ether and separated on an acquity BEH C₁₈ column kept at 40 °C using a mobile phase of 0.1% formic acid in acetonitrile: 0.1% formic acid in de-ionized water (70:30). The flow rate was 0.25 mL/min. Multiple reaction monitoring (MRM) was operated in electrospray (ESI)-positive mode at the ion transition of 418.06 > 165.0 for the analyte and 447.09 > 128.0 for the IS. FDA guidance for bioanalytical method validation was followed in method validation. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.999 with a limit of quantitation of 0.5 ng/mL. Moreover, the metabolic stability of pexidartinib in liver microsomes was estimated. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis III)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Method Development and Validation in Food and Pharmaceutical Analysis III

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (12 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI