Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence Study
Isosorbide-5-mononitrate (5-ISMN), an organic nitrate vasodilator, has been widely used worldwide to prevent angina pectoris for more than two decades. A simple and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the deter...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Analytical Methods in Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2020/1753265 |
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| author | Yinping Zhou Aijing Liu Ranran Jia Mengyi Wu Ni Wu Chunyan Liu Zhihui Han Haitang Hu Hongyun Wang Qing He |
| author_facet | Yinping Zhou Aijing Liu Ranran Jia Mengyi Wu Ni Wu Chunyan Liu Zhihui Han Haitang Hu Hongyun Wang Qing He |
| author_sort | Yinping Zhou |
| collection | DOAJ |
| description | Isosorbide-5-mononitrate (5-ISMN), an organic nitrate vasodilator, has been widely used worldwide to prevent angina pectoris for more than two decades. A simple and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of 5-ISMN in human plasma. 13C6-5-ISMN is an internal standard, and 5-ISMN was extracted from human plasma (50 µL) with ethyl acetate (200 µL) by a simple liquid-liquid extraction method. The chromatographic separation was carried out on LC-20A (Shimadzu, Japan) using an analytical column ZORBAX XDB-C18 (4.6 × 50 mm, 5 µm), coupled with API 4000 tandem mass spectrometers in a multiple reaction monitoring (MRM) mode. The mobile phase was composed of acetonitrile (organic phase A) and 2 mM ammonium acetate in water (aqueous phase B) with an isocratic elution of A/B = 90 : 10 (v/v). The total run time was 3.5 min with a small injection volume (5 µL). This method was fully validated in every aspect of selectivity, linearity, accuracy, precision, matrix effect, extraction recovery, and different stabilities. It was proved that the calibration standards within the 5.00–1000 ng/mL concentration range were linear. The lower limit of quantification was 5.00 ng/mL for 5-ISMN. The intrabatch and interbatch accuracy (RE) ranged from −8.8% to 7.1% with precision between 2.4% and 6.6%. The mean values of 5-ISMN extraction recovery and matrix effect were 87.0% and 102.0%, respectively. The fully validated method was successfully applied for a bioequivalence clinical trial of oral 20 mg 5-ISMN tablets in healthy Chinese subjects. |
| format | Article |
| id | doaj-art-ec629a2c86da48b09fe7b61cacb87a2d |
| institution | DOAJ |
| issn | 2090-8865 2090-8873 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Analytical Methods in Chemistry |
| spelling | doaj-art-ec629a2c86da48b09fe7b61cacb87a2d2025-08-20T03:21:24ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732020-01-01202010.1155/2020/17532651753265Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence StudyYinping Zhou0Aijing Liu1Ranran Jia2Mengyi Wu3Ni Wu4Chunyan Liu5Zhihui Han6Haitang Hu7Hongyun Wang8Qing He9Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100730, ChinaClinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100730, ChinaClinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100730, ChinaClinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100730, ChinaClinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100730, ChinaClinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100730, ChinaLivzon Group Medical Clinical Research Center, Zhuhai 519020, ChinaLivzon Group Medical Clinical Research Center, Zhuhai 519020, ChinaClinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100730, ChinaWuxi People’s Hospital of Nanjing Medical University, Wuxi 214023, ChinaIsosorbide-5-mononitrate (5-ISMN), an organic nitrate vasodilator, has been widely used worldwide to prevent angina pectoris for more than two decades. A simple and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of 5-ISMN in human plasma. 13C6-5-ISMN is an internal standard, and 5-ISMN was extracted from human plasma (50 µL) with ethyl acetate (200 µL) by a simple liquid-liquid extraction method. The chromatographic separation was carried out on LC-20A (Shimadzu, Japan) using an analytical column ZORBAX XDB-C18 (4.6 × 50 mm, 5 µm), coupled with API 4000 tandem mass spectrometers in a multiple reaction monitoring (MRM) mode. The mobile phase was composed of acetonitrile (organic phase A) and 2 mM ammonium acetate in water (aqueous phase B) with an isocratic elution of A/B = 90 : 10 (v/v). The total run time was 3.5 min with a small injection volume (5 µL). This method was fully validated in every aspect of selectivity, linearity, accuracy, precision, matrix effect, extraction recovery, and different stabilities. It was proved that the calibration standards within the 5.00–1000 ng/mL concentration range were linear. The lower limit of quantification was 5.00 ng/mL for 5-ISMN. The intrabatch and interbatch accuracy (RE) ranged from −8.8% to 7.1% with precision between 2.4% and 6.6%. The mean values of 5-ISMN extraction recovery and matrix effect were 87.0% and 102.0%, respectively. The fully validated method was successfully applied for a bioequivalence clinical trial of oral 20 mg 5-ISMN tablets in healthy Chinese subjects.http://dx.doi.org/10.1155/2020/1753265 |
| spellingShingle | Yinping Zhou Aijing Liu Ranran Jia Mengyi Wu Ni Wu Chunyan Liu Zhihui Han Haitang Hu Hongyun Wang Qing He Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence Study Journal of Analytical Methods in Chemistry |
| title | Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence Study |
| title_full | Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence Study |
| title_fullStr | Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence Study |
| title_full_unstemmed | Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence Study |
| title_short | Determination of Isosorbide-5-Mononitrate in Human Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Bioequivalence Study |
| title_sort | determination of isosorbide 5 mononitrate in human plasma by high performance liquid chromatography tandem mass spectrometry and its application to a bioequivalence study |
| url | http://dx.doi.org/10.1155/2020/1753265 |
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