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1.
    
The use of anabolic androgenic steroids (AAS) and other performance enhancing substances can change over time, so there is a need to constantly update what substances are used and can be detected. Six women and 30 men anabolic androgenic steroid users were recruited who filled out an anonymous questionnaire about their use of performance enhancing substances during the past year. Sampling took place on a single occasion and included blood and urine collection. Our aim was to identify which doping agents can be detected in men and women self‐reporting AAS use. The first choice of substances differed between men (testosterone) and women (oxandrolone). The use of growth hormones was reported among men (10%) and women (50%). Growth hormone releasing factors/secretagogs were reported by about ~ 20% in both genders. Nandrolone was the most frequently detected anabolic androgenic steroid even in those who did not report use in the past year. Of the current male testosterone users, 82% exhibited testosterone/epitestosterone (T/E) ratios of > 4. Men with current testosterone use displayed 4‐fold and 6‐fold higher median T/E, respectively, when compared with recent and previous testosterone users (P = 0.0001). Dermal testosterone use in women (n = 2) was not associated with a T/E ratio of > 4, but with supra‐physiological total serum testosterone concentrations. Changes in gonadotropins and hematological parameters were associated with the time of the last anabolic androgenic steroid intake in men, whereas in women these biomarkers were within the normal range. This highlights gender specific differences and indicates the need for additional biomarkers in female athletes.  相似文献   

2.
    
Testosterone treatment stimulates the production of red blood cells and alters iron homeostasis. Thus, we investigated whether the ‘haematological module’ of the athlete biological passport (ABP) used by the World Anti‐Doping Agency can be used to indicate misuse of testosterone. Nineteen eugonadal men received intramuscular injections of either 250 mg Sustanon®, a blend of four testosterone esters, or placebo on days 0 and 21 in a randomized, placebo‐controlleddouble‐blind design. Urine samples and blood samples were collected twice pre‐treatment, at least 5 days apart, and on days 1, 3, 5, 10 and 14 post‐injections to assess steroidal and haematological biomarkers of the ABP. The steroidal profile was flagged suspicious in all Sustanon®‐treated subjects, whereas the haematological profile was flagged suspicious in six out of nine subjects. When both sensitivity and specificity were considered, reticulocyte percentage (RET%) appeared as the best marker of the haematological module for implying testosterone ester misuse. Atypical blood passport samples were used to select time points for further isotope‐ratio mass spectrometry (IRMS) analysis of testosterone and its metabolites in simultaneously collected urine. In addition to the testosterone (T) to epitestosterone (E) ratio, the RET% and OFF‐Score could help identify suspicious samples for more targeted IRMS testing. The results demonstrate that unexpected fluctuations in RET% can indicate testosterone doping if samples are collected 3–10 days after injection. From an anti‐doping perspective, the haematological and steroidal modules of the ABP should complement each other when planning targeted follow‐up testing and substantiating likely misuse of testosterone.  相似文献   

3.
    
Micro‐doping with testosterone (T) is challenging to detect with the current doping tests. Today, the methods available to detect T are longitudinally monitoring of urine biomarkers in the Athlete Biological Passport (ABP) and measuring the isotopic composition of excreted biomarkers to distinguish the origin of the molecule. In this study, we investigated the detectability of a single dose of 100 mg T gel in 8 healthy male subjects. We also studied which biomarkers were most sensitive to T gel administration, including blood biomarkers. The ABP successfully detected T gel administration in all 8 subjects. The most sensitive ratio was 5αAdiol/E, however, all ratios showed atypical findings. Isotope ratio mass spectrometry (IRMS) was performed on 5 subjects and only 2 met all the criteria for a positive test according to the rules set by the World Anti‐Doping Agency (WADA). The other 3 showed inconclusive results. Other markers that were affected by T gel administration, not used for this detection today, were serum dihydrotestosterone (DHT) and T as well as reticulocyte count and percentage in whole blood. miRNA‐122 was not significantly affected by the single T dose. A single dose of 100 mg T gel is possible to detect with today's doping tests. Since a single dose of T gel has an impact on some hematological biomarkers, access to both modules of the ABP when evaluating the athletes' profiles will increase the possibility to detect micro‐doses of T. In addition, serum DHT and T may be a useful addition to the future endocrine module of the ABP.  相似文献   

4.
    
The steroidal module of the Athlete Biological Passport (ABP) aims to detect doping with endogenous steroids, e.g. testosterone (T), by longitudinally monitoring several biomarkers. These biomarkers are ratios combined into urinary concentrations of testosterone and metabolically related steroids. However, it is evident after 5 years of monitoring steroid passports that there are large variations in the steroid ratios complicating its interpretation. In this study, we used over 11000 urinary steroid profiles from Swedish and Norwegian athletes to determine both the inter‐ and intra‐individual variations of all steroids and ratios in the steroidal passport. Furthermore, we investigated if the inter‐individual variations could be associated with factors such as gender, type of sport, age, time of day, time of year, and if the urine was collected in or out of competition. We show that there are factors reported in today's doping tests that significantly affect the steroid profiles. The factors with the largest influence on the steroid profile were the type of sport classification that the athlete belonged to as well as whether the urine was collected in or out of competition. There were also significant differences based on what time of day and time of year the urine sample was collected. Whether these significant changes are relevant when longitudinally monitoring athletes in the steroidal module of the ABP should be evaluated further.  相似文献   

5.
    
To detect doping with endogenous steroids, six urinary steroids are longitudinally monitored in the athlete biological passport (ABP). These steroids include testosterone, etiocholanolone, androsterone, 5α‐androstane‐3α,17β‐diol, 5β‐androstane‐3α,17β‐diol, and the testosterone isomer epitestosterone. It is known that the intake of hormonal contraceptives may interfere with the ABP biomarkers. A previous study showed that athletes using hormonal contraceptives (HCs) display lower urinary epitestosterone concentrations than non‐using athletes. In this study, we analyzed the urinary steroid profile prior to and three months after administration of an oral HC including levonorgestrel and ethinylestradiol (n = 55). The urinary concentrations of all the ABP metabolites decreased after three months, with epitestosterone showing the largest decline (median 6.78 to 3.04 ng/mL, p?0.0001) followed by 5α‐androstane‐3α,17β‐diol (median 23.5 to 12.83 ng/mL, p?0.0001), and testosterone (median 5.32 to 3.66, p?0.0001). Epitestosterone is included in two of the five ratios in the ABP (T/E and 5αAdiol/E), and consequently these ratios increased 1.7‐fold (range 0.27 to 8.50) and 1.26‐fold (range 0.14 to 5.91), respectively. Some of these changes may mimic the changes seen after administration of endogenous steroids leading to atypical findings. Notably, even though participants used the same contraceptive treatment schedule, the HC‐mediated epitestosterone change varied to a large extent (median 0.43‐fold, range 0.06 to 6.5) and were associated with a functional T?C promoter polymorphism in CYP17A1. Moreover, the epitestosterone changes correlated with HC‐induced testosterone and gonadotropins changes in serum, indicating that urinary epitestosterone reflects the androgen load in HC‐using women.  相似文献   

6.
    
The interpretation of athlete biological passport (ABP) is strengthened by understanding the natural fluctuations in its biological parameters. Here we have assessed the influence of the menstrual cycle on the hematological module of the ABP. Seventeen women with regular menses were included. Blood samples were collected once a week for two consecutive cycles and analyzed for hematological parameters. Menstrual phases were hormonally determined. The intra‐individual variation in the hematological parameters was similar between the two cycles. Reticulocyte percentage was significantly lower in the follicle phase (median 0.95%) than in the ovulatory (median 1.10%) and luteal phases (median 1.16%), P = 0.006, whereas no differences were found in hemoglobin concentration, hematocrit, red blood cell count, or red blood cell indices. When the values were entered into the ABP model, findings outside the program‐calculated individual thresholds were identified in two participants. One woman showed an atypical low OFF‐score in the last sample collected, mainly because of increased reticulocyte percentage. This was likely a response to treated insufficient iron stores. One woman displayed an atypical hemoglobin value at the lower limit 2 weeks after ovulation, which was likely due to fluctuations in plasma volume. In conclusion, the ABP parameters in general are stable throughout the menstrual cycle. Significant differences between the menstrual phases were found in reticulocytes; however, the variation was not related to findings outside the individual thresholds, except in one individual. Moreover, our results highlight the importance of having information about iron supplementation available when evaluating hematological passports.  相似文献   

7.
    
Today's doping tests involve longitudinal monitoring of urinary steroids including the testosterone glucuronide and epitestosterone glucuronide ratio (T/E) in an Athlete Biological Passport (ABP). The aim of this study was to investigate the possible influence of short‐term use of codeine on the urinary excretion of androgen metabolites included in the steroidal module of the passport prior to and after the co‐administration with testosterone. The study was designed as an open study with the subjects being their own control. Fifteen healthy male volunteers received therapeutic doses of codeine (Kodein Meda) for 6 days. On Day 3, 500 mg or 125 mg of testosterone enanthate (Testoviron®‐Depot) was administered. Spot urine samples were collected for 17 days, and blood samples were collected at baseline, 3, 6, and 14 days after codeine intake. The circulatory concentration of total testosterone decreased significantly by 20% after 3 days' use of codeine (p = 0.0002) and an atypical ABP result was noted in one of the subjects. On the other hand, the concomitant use of codeine and testosterone did not affect the elevated urinary T/E ratio. In 75% of the individuals, the concentration of urinary morphine (a metabolite of codeine) was above the decision limit for morphine. One of the participants displayed a morphine/codeine ratio of 1.7 after codeine treatment, indicative of morphine abuse. In conclusion, our study shows that codeine interferes with the endogenous testosterone concentration. As a result, the urinary steroid profile may lead to atypical findings in the doping test.  相似文献   

8.
    
To detect doping with pseudo-endogenous anabolic steroids in sports, a urinary steroid profile with glucuronidated plus unconjugated androgens is used. In addition to analyze androgen glucuronide metabolites, it can be of interest to also include sulfate metabolites in the urinary steroid profile. The combined ratios of epitestosterone sulfate/epitestosterone glucuronide to the ratios of testosterone sulfate/testosterone glucuronide ((ES/EG)/(TS/TG)) have previously been investigated as a complementary biomarker for testosterone doping. In this restudy, the aim was to evaluate this biomarker in a larger study sample population. A single dose of 500-mg testosterone enanthate was administered to 54 healthy male volunteers. Urine was collected prior to (Day 0) administration and throughout 15 days and analyzed for the sulfate and glucuronide conjugates of testosterone and epitestosterone. The results show that the combined ratio increased to a larger extent than the traditional T/E ratio in all subjects. This increase was independent on UGT2B17 gene polymorphism. Moreover, a delayed peak of the combined ratio was observed in ~60% of the participants. The results confirm that complementary analyses of the sulfate metabolites may be a useful approach to detect testosterone doping in men.  相似文献   

9.
    
Every year, the World Anti‐Doping Agency (WADA) publishes the main statistics reported by the accredited laboratories, which provide very valuable information for assessing changes in the patterns of doping in sports over time. Using the information provided since 2003 as the basis for the analysis, the evolution of doping/anti‐doping figures over the last decade can be examined in reasonable detail, at least in reference to samples analyzed and categories of substances more commonly found in athletes' samples. This brief analysis of the WADA statistical reports leads us to the following outcomes: the increase in anti‐doping pressure from 2003 to 2015, as evidenced by increased numbers of samples analyzed and banned substances, has not directly produced a higher frequency of adverse/atypical findings. Although this could be interpreted as steady state in the capacity to detect doping through this whole period, it also resulted in a significant increase in the absolute number of samples catalogued as doping (from 2247 in 2003 to 5912 in 2015). Anabolic agents have been the most common doping substances detected in all statistics reports while the remaining groups of substances are much less frequently found in doping control samples. Given that one might have expected the enhancement of the anti‐doping programme led by WADA over this last decade to have increased the percentage of adverse/atypical findings, the fact that it did not might indicate the need to take another step in sampling strategies, such as ‘more intelligent testing’ based on the differences in the prevalence of doping substances among sports. Copyright © 2017 John Wiley & Sons, Ltd.  相似文献   

10.
    
Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti‐doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double‐blinded, placebo‐controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin β) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl‐PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl‐PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl‐PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings.  相似文献   

11.
    
This study investigated the impact of low-volume blood withdrawal on the hematological biomarkers currently considered for anti-doping purposes. After baseline measurement (D − 7), a 140 mL blood withdrawal was completed (D + 0) on 12 healthy volunteers, followed by weekly monitoring for 21 days (D + 7 – 21). Each visit consisted of a full blood count (Sysmex XN-1000) and duplicate blood volume measurements by CO-rebreathing. A significant decrease in total hemoglobin mass (Hbmass) (−2.3%, p = 0.007) and red blood cell volume (RBCV) (−2.8%, p = 0.028) was reported at D + 7. Despite no atypical passport finding (ATPF) when considering the athlete biological passport adaptive longitudinal model, hemoglobin concentration ([Hb]) increased significantly at D + 21 (+3.8%, p = 0.031). Besides, ferritin (FERR) was significantly downregulated at all points following blood withdrawal, with the largest decrease occurring at D + 7 (−26.6%, p < 0.001). Regardless of the presumable effect of blood reinfusion on ABP biomarkers, these results illustrate the challenge of monitoring hematological variables for the detection of low-volume blood withdrawal. Finally, this study outlines the sensitivity of FERR to altered erythropoiesis to support the implementation of iron markers as complementary variables for the longitudinal monitoring of blood doping, despite the potential influence of confounding factors (e.g., iron supplementations).  相似文献   

12.
    
To analyze doping control samples from female athletes demands understanding of non-doping factors that affect the steroid profile. These could be physiological factors such as exercise, alcohol consumption, hormonal changes during the menstrual cycle, or the effect of commonly used approved drugs like combined oral contraceptives. Urine samples have been the main way of doping testing, but serum samples are proposed as a complement. Testosterone, dihydrotestosterone, or the ratio of testosterone and androstenedione has been proposed as a biomarker for testosterone doping because it increases after transdermal testosterone administration. In this double-blind, randomized, placebo-controlled study of 340 healthy females, we analyzed the serum steroid levels, including glucuronide metabolites, before and after 3 months of combined oral contraceptives or placebo. At follow up, sample collection in the placebo group was randomly distributed between different menstrual cycle phases. This enabled to analyze changes in concentrations between the follicular, ovulation, and luteal phases. Combined oral contraceptives decreased all serum steroids including the glucuronide metabolites. As expected, serum testosterone levels increased during the ovulation phase, and also androstenedione and androstenediol, whereas the glucuronide metabolites remained unaffected. Neither combined oral contraceptives nor menstrual cycle phases did affect the ratio of testosterone and androstenedione in serum, and consequently this ratio seems promising as a marker of doping with endogenous anabolic androgenic steroids in women.  相似文献   

13.
    
This study evaluated whether recombinant human erythropoietin (rhEpo) treatment combined with chronic hypoxia provided an additive erythropoietic response and whether the athlete biological passport (ABP) sensitivity improved with hypoxia. Two interventions were completed, each containing 4 weeks baseline, 4 weeks exposure at sea level or 2,320 m of altitude, and 4 weeks follow-up. Participants were randomly assigned to 20 IU·kg bw−1 rhEpo or placebo injections every second day for 3 weeks during the exposure period at sea level (rhEpo n = 25, placebo n = 9) or at altitude (rhEpo n = 12, placebo n = 27). Venous blood was analyzed weekly. Combining rhEpo and hypoxia induced larger changes compared with rhEpo or hypoxia alone for [Hb] (p < 0.001 and p > 0.05, respectively), reticulocyte percentage (p < 0.001), and OFF-hr score (p < 0.01 and p < 0.001, respectively). The most pronounced effect was observed for reticulocyte percentage with up to ~35% (p < 0.001) and ~45% (p < 0.001) higher levels compared with rhEpo or hypoxia only, respectively. The ABP sensitivity for the combined treatment was 54 and 35 percentage points higher for [Hb] (p < 0.05) and reticulocyte percentage (p < 0.05), respectively, but similar for OFF-hr score, compared with rhEpo at sea level. Across any time point, [Hb] and OFF-hr score combined identified 14 unique true-positive participants (56%) at sea level and 12 unique true-positive participants (100%) at altitude. However, a concurrent reduction in specificity existed at altitude. In conclusion, rhEpo treatment combined with hypoxic exposure provided an additive erythropoietic response compared with rhEpo or hypoxic exposure alone. Correspondingly, ABP was more sensitive to rhEpo at altitude than at sea level, but a compromised specificity existed with hypoxic exposure.  相似文献   

14.
    
Reticulocytes (Ret) are a key variable in the emerging concept of the athlete's biological passport and the longitudinal monitoring of biological parameters in the field of anti-doping. In this context, knowledge on the variability of Ret in athletes and the influence of exercise is necessary. The aim of the present study was to evaluate longitudinal variation in Ret and the influence of short- and long-term exercise.Ret% in 793 samples of 238 athletes were determined and analyzed in different study parts for inter- and intra-individual variation and the impact of long- (competitive season) and short-term (all out) exercise.Median Ret% was 0.9 (CI(0.5-99.5%) 0.4-2.7). Intra-individual variation for Ret% was 0.0118; inter-individual variation 0.0124. During periods of intensive exercise Ret% was slightly lower (mean - 0.1%, p = 0.048). After a short, all-out exercise bout, Ret% was increased (+0.5%, p = 0.0028).Athletes mostly display similar Ret% than the normal population; however, intra-individual variation in athletes is higher. During the competitive season of endurance athletes, Ret% is slightly decreased. After short bouts of intense exercise Ret% is increased. These data can be used for the interpretation of blood profiles in athletes.  相似文献   

15.
    
Exposure to either natural or simulated hypoxia induces hematological adaptations that may affect the parameters of the Athlete Biological Passport (ABP). The aim of the present study was to examine the effect of a novel, mixed hypoxic dose protocol on the likelihood of producing an atypical ABP finding. Ten well‐trained middle‐distance runners participated in a “live high, train low and high” (LHTLH) altitude training camp for 14 days. The participants spent ?6 hr.d‐1 at 3000–5400 m during waking hours and ?10 h.d‐1 overnight at 2400–3000 m simulated altitude. Venous blood samples were collected before (B0), and after 1 (D1), 4 (D4), 7 (D7), and 14 (D14) days of hypoxic exposure, and again 14 days post exposure (P14). Samples were analyzed for key parameters of the ABP including reticulocyte percentage (Ret%), hemoglobin concentration ([Hb]), and the OFF‐score. The ABP adaptive model was administered at a specificity of 99% to test for atypical findings. We found significant changes in [Hb] and Ret% during the hypoxic intervention. Consequently, this led to ABP threshold deviations at 99% specificity in three participants. Only one of these was flagged as an “atypical passport finding” (ATPF) due to deviation of the OFF‐score. When this sample was evaluated by ABP experts it was considered “normal”. In conclusion, it is highly unlikely that the present hypoxic exposure protocol would have led to a citation for a doping violation according to WADA guidelines.  相似文献   

16.
    
The athlete biological passport (ABP) was implemented by the International Cycling Union (UCI) in 2008. However, this improvement in the fight against doping was preceded with different milestones since 1996. In this paper, a detailed evolution of the ABP from traditional direct (urine) testing for antidoping purposes is presented. A chronological overview of the ABP including earlier non‐disclosed information and contemporary documentation are shown and documented. The strategic development from on‐site competition blood testing, called “health tests”, to the structure of the ABP is explained in this historical overview which provides information to the antidoping community and general public regarding the beginning of blood doping tests.  相似文献   

17.
    
The steroidal module of the athlete biological passport (ABP) introduced by the World Anti‐Doping Agency (WADA) in 2014 includes six endogenous androgenic steroids and five of their concentration ratios, monitored in urine samples collected repeatedly from the same athlete, whose values are interpreted by a Bayesian model on the basis of intra‐individual variability. The same steroid profile, plus dihydrotestosterone (DHT) and DHEA, was determined in 198 urine samples collected from an amateur marathon runner monitored over three months preceding an international competition. Two to three samples were collected each day and subsequently analyzed by a fully validated gas chromatography–mass spectrometry protocol. The objective of the study was to identify the potential effects of physical activity at different intensity levels on the physiological steroid profile of the athlete. The results were interpreted using principal component analysis and Hotelling's T2 vs Q residuals plots, and were compared with a profile model based on the samples collected after rest. The urine samples collected after activity of moderate or high intensity, in terms of cardiac frequency and/or distance run, proved to modify the basal steroid profile, with particular enhancement of testosterone, epitestosterone, and 5α‐androstane‐3α,17β‐diol. In contrast, all steroid concentration ratios were apparently not modified by intense exercise. The alteration of steroid profiles seemingly lasted for few hours, as most of the samples collected 6 or more hours after training showed profiles compatible with the “after rest” model. These observations issue a warning about the ABP results obtained immediately post‐competition.  相似文献   

18.
    
The detection of testosterone intake is facilitated by monitoring the urinary steroid profile in the athlete biological passport. This technique can be used with confidence to identify target samples for isotope ratio mass spectrometry. Regrettably, most research has been performed on male subjects resulting in a method that does not account for females' steroid concentration and/or variation. This study evaluates the usefulness of the carbon isotope ratio (CIR) in serum of female subjects. Two steroid sulphates are targeted in serum, androsterone and epiandrosterone. Both exhibit statistically significant depletion of their CIR after 10 weeks of daily (10 mg) transdermal testosterone administration. Of the 21 female subjects, samples from six individuals were identified as adverse analytical findings; additionally, four were found atypical considering the serum CIR. The urinary athlete biological passport was not sufficiently sensitive to identify target serum samples for isotope ratio mass spectroscopy. Of the six with a suspicious passport, only two could be confirmed using the serum CIR of androsterone and epiandrosterone. This study shows that CIR analysis in serum cannot be considered the sole confirmatory solution to detect testosterone doping in women due to low sensitivity. However, this analysis has the potential to be used as a complementary method in certain situations to confirm exogenous testosterone in women.  相似文献   

19.
    
The steroid profile (SP) is a powerful tool to detect the misuse of endogenous anabolic androgenic steroids in sports, and it is included in the Athlete Biological Passport (ABP). Glucocorticoids (GCs), which are widely prescribed in sports and only prohibited in competition by systemic routes, inhibit the hypothalamic‐pituitary‐adrenal axis. Since the metabolites monitored in the SP have a partial adrenal origin, their excretion in urine might be altered by GCs consumption. The aim of the present work was to investigate if GCs administered by either systemic or local routes could influence the SP parameters. Three of the most frequently detected GCs in sports (prednisolone, betamethasone, and triamcinolone acetonide) were administered to healthy male and female volunteers (n=40) using different administration routes (topical, oral, and intramuscular administration at different doses). In total, 66 administrations of GCs were performed. Urine samples were collected before and after GCs administration. The SP was measured using gas chromatography‐mass spectrometry. The excretion rates of the SP metabolites decreased after systemic GCs administration. This excretion decrease showed to be associated with the dose and the administration route. However, the individual evaluation of the SP ratios (T/E, A/T, A/Etio, 5αAdiol/5βAdiol, and 5αAdiol/E) led to normal sequences for all the conditions tested. Therefore, GCs administration did not produce misinterpretations on the ABP evaluation. According to these results, GCs administration should not distort the establishment of normal ranges of the SP ratios, and does not need to be considered a confounding factor in the SP evaluation.  相似文献   

20.
    
An analytical procedure based on ultra‐performance liquid chromatography‐mass spectrometry was developed to screen and to confirm dutasteride and its metabolites in human urine. Sample preparation included an enzymatic hydrolysis followed by solid‐phase extraction using the strong cation exchange cartridges OASIS® MCX. The chromatographic separation was carried out on C18 column, employing as mobile phases ultra purified water and acetonitrile, both containing 0.1% formic acid. Detection was achieved using a triple quadrupole as a mass spectrometric analyzer, with positive ion electrospray ionization and multiple reaction monitoring as acquisition mode. The analytical procedure developed was validated according to ISO 17025 and World Anti‐Doping Agency guidelines. The extraction efficiency was estimated to be greater than 75% for both dutasteride and its hydroxylated metabolites. Detection capability was determined in the range of 0.1–0.4 ng/mL. Specificity and repeatability of the relative retention times (CV% < 0.5) and of the relative abundances of the characteristic ion transitions selected (CV% < 10) were confirmed to be fit for purpose to ensure the unambiguous identification of dutasteride and its metabolites in human urine. The developed method was used to characterize the urinary excretion profile of dutasteride after both chronic and acute administration of therapeutic doses. After chronic administration, dutasteride and its hydroxylated metabolites were easily detected and confirmed. After acute administration, instead, only the two hydroxylated metabolites were detected for 3–4 days.  相似文献   

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