Dataset Information

RP-HPLC method validation for fast extraction and quantification of Levonorgestrel drug from silicone based intrauterine device intended for in-process and finished formulation.

ABSTRACT:

Background

To develop and validate a simple and consistent reversed phase high performance liquid chromatography (RP-HPLC) method for the estimation of Levonorgestrel (LNG) drug from silicone based intrauterine device.

Methods

Sample solution was prepared using tetrahydrofuran (THF) as solvent for the drug extraction, and RP-HPLC analysis was performed using Luna C18 analytical column (150 × 4.6 mm, 5 μm, 100 Å - Phenomenex), with a mobile phase consisting of a mixture of acetonitrile and water (50:50, v/v) at a flow rate of 1.0 ml/min and injection volume of 20 μl. Detection was carried out at 241 nm in PDA detector, with a total run time of 15 min. The method was validated in accordance with ICH guidelines. Method applicability was tested for optimizing formulation using quality-by-design approach, to check the stability and content uniformity of levonorgestrel-silicone mixture (core blend), and quantifying the amount of LNG from commercially available silicone based formulation.

Results

The retention time for LNG drug was obtained at 8.5 min (± 0.3 min). A linear relationship was observed over the concentration range of 2.6-15.6 μg/ml with the correlation coefficient (r) value 0.9999. The method was found to be precise within the acceptable limit (RSD < 2%) and the drug recovery from the intrauterine device was found in the range 99.78-100.0%. Content uniformity for different prototypes developed was observed in the range of 91.6-101.4%, and assay of optimized core blend was in the range of 97.78-106.79% during the 10 days of retention period for stability studies.

Conclusion

The validated method is found to be a simple, accurate, precise, reproducible, and hence can be used for the routine analysis of LNG such as in-process, quality control and stability assays of silicone based intrauterine devices by RP-HPLC.

SUBMITTER: Veeran MG

PROVIDER: S-EPMC8149566 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

RP-HPLC method validation for fast extraction and quantification of Levonorgestrel drug from silicone based intrauterine device intended for in-process and finished formulation.

Veeran Midhu George MG C Karthikeyan K B Bharaniraja B Painuly Diksha D Aprem Abi Santhosh AS

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 20210501 1

<h4>Background</h4>To develop and validate a simple and consistent reversed phase high performance liquid chromatography (RP-HPLC) method for the estimation of Levonorgestrel (LNG) drug from silicone based intrauterine device.<h4>Methods</h4>Sample solution was prepared using tetrahydrofuran (THF) as solvent for the drug extraction, and RP-HPLC analysis was performed using Luna C18 analytical column (150 × 4.6 mm, 5 μm, 100 Å - Phenomenex), with a mobile phase consisting of a mixture of acetonit ...[more]

PMID: 33934266

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Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.

Project description:ObjectiveTo evaluate heavy menstrual bleeding treatment outcomes with levonorgestrel 52-mg intrauterine device (IUD) use in participants without body mass index (BMI) or parity restrictions.MethodsInvestigators included participants aged 18-50 years with no pelvic or systemic pathology causing heavy menstrual bleeding at 29 U.S. centers in a prospective trial. Participants had up to three screening cycles with menstrual product collection for alkaline hematin blood-loss measurements. Investigators enrolled those with two menses with blood loss of 80 mL or more (values averaged for baseline blood loss), placed the IUD, and followed participants for up to six 28-day cycles. Participants collected any menstrual products used during cycles 3 and 6 for blood-loss measurement. We evaluated outcomes in participants with at least one follow-up assessment for the primary outcome of median absolute blood-loss change and, secondarily, treatment success , defined as the proportion with a final measured blood loss less than 80 mL and at least 50% reduction from baseline. We evaluated exploratory outcomes of differences in blood-loss changes by BMI and parity using Wilcoxon rank sum test.ResultsOf 105 enrolled participants, 47 (44.8%) had obesity (BMI 30.0 or higher) and 29 (27.6%) were nulliparous. Baseline mean blood loss ranged from 73 to 520 mL (median 143 mL, interquartile range 112-196 mL). Eighty-nine (84.8%) had at least one evaluable follow-up evaluation. Participants had median (interquartile range) absolute blood-loss decreases at cycles 3 (n=86) and 6 (n=81) of 93.3% (86.1-97.7%) and 97.6% (90.4-100%), respectively. At cycle 6, participants without obesity (n=43) and with obesity (n=38) had similar median [interquartile range] decreases (97.6% [91.8-100%] and 97.5% [90.3-100%], respectively; P =.89), with comparable findings for nulliparous (n=25) and parous (n=56) participants (97.0% [91.7-99.1%] and 98.1% [89.9-100%], respectively; P =.43). Treatment success occurred in 81.8% (95% CI 74.2-89.4%) of 99 participants, excluding those with no outcomes due to lost to follow-up or consent withdrawal, and did not vary by BMI or parity. The most common adverse events leading to discontinuation were bleeding or cramping (n=6 [5.7%]) and expulsion (n=5 [4.8%]).ConclusionThis levonorgestrel 52-mg IUD reduces blood loss by more than 90% over 6 months compared with baseline for most users with heavy menstrual bleeding.Funding sourceMedicines360.Clinical trial registrationClinicalTrials.gov , NCT03642210.

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Project description:ObjectivesTo estimate the hazard of incident idiopathic intracranial hypertension, a potentially blinding condition, among women using levonorgestrel intrauterine devices (LNG-IUD) compared to copper IUD, as conflicting associations have been reported.Study designThis retrospective, longitudinal cohort study identified women ages 18-45 years in a large care network (January 1, 2001, to December 31, 2015) using LNG-IUD, subcutaneous etonogestrel implant, copper IUD, tubal device/surgery, or hysterectomy. Incident idiopathic intracranial hypertension was defined as the first diagnosis code for after 1 year without any codes and following brain imaging or lumbar puncture. Kaplan-Meier analysis estimated time-dependent probabilities of idiopathic intracranial hypertension at 1 and 5 years after incident contraception use, stratified by type. Cox regression estimated the hazard of idiopathic intracranial hypertension associated with LNG-IUD use compared to copper IUD (primary comparison) after adjusting for sociodemographics and factors associated with idiopathic intracranial hypertension (e.g., obesity) or contraception selection. A sensitivity analysis with propensity score-adjusted models was performed.ResultsOf 268,280 women, 78,175 (29%) used LNG-IUD, 8715 (3%) etonogestrel implant, 20,275 (8%) copper IUD, 108,216 (40%) hysterectomy, 52,899 (20%) tubal device/surgery, and 208 (0.08%) developed idiopathic intracranial hypertension over a mean follow-up of 2.4 ± 2.4 years. Also, 1-/5-year Kaplan-Meier idiopathic intracranial hypertension probabilities were 0.0004/0.0021 for LNG-IUD and 0.0005/0.0006 for copper IUD users. LNG-IUD use did not show significantly different hazard of idiopathic intracranial hypertension compared to copper IUD (adjusted hazard ratio 1.84 [95% CI 0.88, 3.85]). Sensitivity analyses were similar.ConclusionsWe did not observe a significantly increased hazard of idiopathic intracranial hypertension among women using LNG-IUD compared to copper IUDs.ImplicationsThe lack of an association between LNG-IUD use and idiopathic intracranial hypertension in this large observational study provides reassurance to women considering initiation or continued use of this highly effective contraceptive method.

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Dataset Information

RP-HPLC method validation for fast extraction and quantification of Levonorgestrel drug from silicone based intrauterine device intended for in-process and finished formulation.

Background

Methods

Results

Conclusion

Publications

RP-HPLC method validation for fast extraction and quantification of Levonorgestrel drug from silicone based intrauterine device intended for in-process and finished formulation.

Similar Datasets

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