Application of UPLC–MS/MS for separation and quantification of 3α-Hydroxy Tibolone and comparative bioavailability of two Tibolone formulations in healthy volunteers

Shinde, Vijay P.; Pudage, Ashutosh; Jangid, Arvind G.; Mistri, Hiren N.; Patel, Pratik K

doi:10.1016/j.jpha.2013.02.006

Cited by 7 publications

(2 citation statements)

References 15 publications

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“…Tibolone effectively relieves menopause-related symptoms and prevents osteoporosis [ 12 ] and is recommended for treating postmenopausal women [ 13 ] . The purpose of this study was to evaluate the effect of low dose tibolone therapy on the ovarian area, uterine volume and endometrial thickness by transvaginal ultrasound at three defined intervals, and investigate the optimum cut-off value of endometrial thickness for curettage at uterine bleeding.…”

Section: Introductionmentioning

confidence: 99%

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

et al. 2016

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The aim of this study was to evaluate the effects of low-dose tibolone therapy on ovarian area, uterine volume and endometrial thickness, and define the cut-off value of endometrial thickness for curettage during uterine bleeding. We followed 619 postmenopausal women, aged 40-60 years, for two years. There were 301 subjects in the low-dose tibolone treatment group and 318 subjects in the control group. The ovarian area, uterine volume and endometrial thickness in all participants were measured by transvaginal ultrasound prior to, one and two years post enrollment, respectively. Endometrial specimens were collected from all subjects with abnormal uterine bleeding during the follow-up period. We found that the uterine volume in the treatment group was greater than that in the control group, and the difference was significant (P<0.05), but there were no significant differences in ovarian area and endometrial thickness between the two groups (P>0.05). When the cut-off value for endometrial thickness was 7.35 mm, the sensitivity and specificity were 100% and 79.07%, respectively, and 85.71% and 93.02% when 7.55 mm was set as the cut-off during tibolone therapy. The results indicate that low-dose tibolone therapy may postpone uterine atrophy and the cut-off value of endometrial thickness may be appropriately adjusted for curettage.

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Section: Introductionmentioning

confidence: 99%

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

et al. 2016

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“…A novel, fast, robust and precise method was developed for the separation and quantification of 3α-hydroxy tibolone bioavailability of its formulations in humans by utilizing UPLC-MS technology. The analyte extraction was carried out through liquidliquid extraction from plasma [11]. This method was a landmark in explaining various pharmacokinetic as well as bioequivalence parameters for tibolone as well as for other drugs.…”

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confidence: 99%

UPLC-MS: A Powerful Tool in Analytical Research

Rawal¹

2018

MACIJ

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The emergence of ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry (MS) as an alternative to traditional high-performance liquid chromatography techniques is a powerful technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectroscopy with significant gains in resolution and sensitivity and marked reductions in the overall time of analysis [1]. UPLC is an advanced technique which consists of narrow bore columns with very fine packing materials (approximate particle size: 1.7μm) and the mobile phases are introduced at ultrahigh pressures [2]. The typical UPLC instrument is designed in such a way that the integrated system from pump (withstand a pressure up to 15000 psi) to auto sampler, heater, detector, software are fully compatible with the small particle technology [3]. Due to this advancement, ultra-sensitive responses are obtained and ultimately detection sensitivity by MS is enhanced [4]. UPLC-MS technique has tremendous applications in various analytical procedures which include: toxicity analysis, analysis of food stuffs, beverages, identification of drug metabolites in biological samples, for simultaneous extraction and screening of diuretics, betablockers, steroids in human fluids, Functional Genomic Studies and multi-residue analysis of pharmaceuticals in waste water etc.

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Quantification of 3α-hydroxytibolone in human plasma by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS): Application in a bioequivalence study in healthy postmenopausal volunteers

Portela

Laurito

Severino

et al. 2016

Analytical Chemistry Research

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A sensitive, specific and fast method to quantify 3α-hydroxytibolone in human plasma using deuterated 3α-hydroxytibolone (d5) as internal standard is described. The analyte and the internal standard were extracted from plasma (900 μL) by liquid-liquid extraction using ethyl ether/hexane (50/50, v/v) and ammonium hydroxide (50%). The extracts were analyzed by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry without derivatization. Chromatography was performed isocratically on a Gemini-NX™ C18 5 μm (150 × 4.6 mm i. d.) column. The method had a chromatographic run time of 3.75 min and a linear calibration curve over the range 1–100 ng/mL. The limit of quantification validated was 1 ng/mL. This method was used to assess the bioequivalence between two different tibolone oral formulations: Livolon (1.25 mg tablet) provided by Biolab Sanus Farmacêutica (Brazil), as the test formulation, and Libiam™ (1.25 mg tablet) produced by Libbs Farmacêutica (Brazil), as the reference formulation. A single 3.75 mg dose of each formulation was administered to 46 postmenopausal female healthy volunteers. The study was conducted in an open, randomized, two-period crossover balanced design with a 2 week washout interval between the doses. The 90% confidence interval for Cmax, AUC(0-last) and AUC(0-inf) individual test/reference ratios were 97.48–111.51, 95.35–103.20 and 96.42–103.86, respectively. It is concluded that Livolon (1.25 mg tablet) is bioequivalent to Libiam™ (1.25 mg tablet), with regards to both rate and extent of absorption

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Application of UPLC–MS/MS for separation and quantification of 3α-Hydroxy Tibolone and comparative bioavailability of two Tibolone formulations in healthy volunteers

Cited by 7 publications

References 15 publications

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

UPLC-MS: A Powerful Tool in Analytical Research

Quantification of 3α-hydroxytibolone in human plasma by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS): Application in a bioequivalence study in healthy postmenopausal volunteers

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