Development and validation of simultaneous assay of simvastatin, beta-hydroxy simvastatin as metabolite in human plasma using liquid chromatography-tandem mass spectrometry

Original Research

Abstract

Introduction: Several generic products containing simvastatin are circulating on the Vietnamese market at a more inexpensive price than that of a brand-name one. These formulations, however, have not been assessed for in vivo bioequivalence to the reference product. After oral administration, simvastatin (SIM) is extensively converted into an active metabolite, beta-hydroxy simvastatin acid (SIM-A) and a very low concentration of simvastatin can be found in plasma. Therefore, a method for quantification of simvastatin and its metabolite needs to be developed with a high specificity and sensitivity to detect these analytes in human plasma at such low concentrations. Our purpose was to develop a reliable LC-MS/MS (liquid chromatography-tandem mass spectrometry) method for simultaneous determination of simvastatin and metabolite of simvastatin, beta-hydroxy simvastatin acid, in human plasma and to apply this method to evaluate the bioequivalence of a test product in comparison with the reference product.

Methods: Mass spectrometry, internal standard (IS), and chromatographic conditions were investigated to find out the suitable IS and conditions. Human plasma samples were treated by liquid-liquid extraction (LLE). The assay was validated in compliance with US-FDA (United States-Food and Drug Administration), and EMA (European Medicines Agency) guidelines.

Results: LC-MS/MS with electrospray ionization interface in positive (for SIM and lovastatin as IS) and negative (for SIM-A) ionization mode performed under the multiple reaction monitoring mode was used for detection of the analytes. The transition of m/z is 436.00 → 285.15, 435.10 → 319.15, and 404.95 → 199.10 for SIM, SIM-A, and IS, respectively. Tert-buthyl methyl ether was used for extraction of analytes from human plasma by a simple LLE followed by addition of an ammonium acetate buffer. The developed method was fully validated with acceptable selectivity, linearity and linear range, matrix effect, lower limit of quantitation (LLOQ), carryover, dilution integrity, and intra- and inter-day accuracy and precision, free-thaw stability.

Conclusions: The method can be applied for quantification of these compounds in human plasma for in vivo bioavailability and bioequivalence studies. 

Graphical abstract

The Vietnamese version of the constitution in Chinese medicine questionnaire (CCMQ): validity and reliability

Original Research

Abstract

Introduction: Body constitution (BC) plays an important role in preserving health and reducing risk of diseases depending on each person’s physical characteristics. Classification of BC is almost based on the Constitution in Chinese Medicine Questionnaire (CCMQ). In Vietnam, there is still no questionnaire survey to assess the BC. Therefore, this study aims to adapte and validate the Vietnamese version of CCMQ.

Methods: 2 phases of the study: the first phase constituted the translation with cross-cultural adaptation of CCQM into Vietnamese according to Guillemin et al; the second phase assessed the reliability and validity of the Vietnamese CCMQ version based on a cross-sectional study.

Results: Phase 1 formed the final Vietnamese CCMQ version in which face validity and content validity are incorporated. Seven traditional medicine practitioners confirmed the content validity (CVI: 57%–100%). The face validity of the scale is qualified. In phase 2, 455 participants aged 18 years old or older were enrolled in this study from 01/2021 – 06/2021 in Ho Chi Minh City. Regarding the criterion validity, the correlation coefficient between Vietnamese CCMQ and SF-36 was 0.67 for the Neutral type and -0.31 to -0.57 for the rest. The internal consistency varied from 0.70 to 0.83 measured by Cronbach’s alpha. The test-retest reliability varied from 0.63 to 0.90 for each of the 9 sub-scales and from 0.40 to 0.68 for each of the 60 questions.

Conclusions: The Vietnamese version of CCMQ has good reliability and validity, which provides a strong basis for future researches on BC of Vietnamese Traditional Medicine. 

Graphical abstract

Contraceptive use and associated factors among postpartum women from 0 to 6 months in Trang Bom District, Dong Nai Province, Vietnam

Original Research

Abstract

Introduction: Well-timed contraception after delivery using effective methods protects women from unintended pregnancies and improves the quality of life of both women and their children. However, little attention has been paid on the issue in Vietnam. Therefore, this study aimed to determine the percentage of postpartum women from 0 to 6 months using contraceptive methods and associated factors in Trang Bom District, Dong Nai Province, Vietnam.

Methods: A cross-sectional study was adopted. A systematic random sampling method was used to select 355 postpartum women. Women were interviewed about sociodemographic characteristics, reproductive history, and contraceptive use after giving birth.

Results: Of the 355 women, 63.1% used at least one modern or traditional contraceptive method; 58.9% current use, 4.2% previous use, and 36.9% never use. The most selected methods were withdrawal (41.1%), male condom (28.2%), and calendar method (24.4%). Multivariable analysis showed that women who had their menstruation returned, long postpartum duration, high education level, many years of marriage, and previous caesarean section were more likely to use contraception after birth.

Conclusion: The family planning program in Vietnam should focus more on postpartum women. Postpartum contraception should be consulted at all obstetric health centers before and right after delivery. Emphasis should be placed on the initial times to adopt contraception soon and not waiting until the first menses. Women should be encouraged to use modern contraceptive methods instead of traditional ones.
 

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