This is a working overview of LC-MS/MS, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-08-19. Anything still debated is marked as such rather than presented as settled.
Clinical development stopped after rodent studies showed tumors at multiple sites. Whether those findings predict human cancer risk remains an open question, but they led sponsors to discontinue programs. Human safety data are limited to small, short-term studies that were not designed to assess cancer risk. Reported effects in those studies included changes in blood lipids, but the evidence is insufficient for medical use. Long-term consequences of nonmedical use are not well characterized. Questions about dose, duration, and individual susceptibility remain unresolved.
Cardarine is a common name for GW501516, an investigational compound developed in the 1990s for metabolic conditions. It acts as an agonist at peroxisome proliferator-activated receptor delta, a nuclear receptor involved in lipid and energy metabolism. The compound is frequently mislabeled as a selective androgen receptor modulator, or SARM, but its molecular target is different. GW501516 reached early clinical testing before development was discontinued. It has no approved therapeutic use in any country. The name cardarine is not a formal international nonproprietary name.
Sporting authorities added GW501516 to prohibited lists after it appeared in athlete samples and online markets. The World Anti-Doping Agency classifies it as a hormone and metabolic modulator, and its use can lead to an anti-doping rule violation. Some early laboratory work suggested effects on fatty acid oxidation and endurance-related metabolism in animals, but those findings do not establish safe or effective use in people. Reports of adverse events in humans are scarce and often anecdotal, which complicates risk assessment.
Legal status varies by country. In some places, cardarine is controlled under medicines or psychoactive substances laws; in others, it may be sold with minimal oversight as a research chemical. Customs agencies have intercepted shipments, and several national health agencies have issued warnings about products marketed for bodybuilding or performance enhancement. The lack of a standardized pharmaceutical supply means identity, purity, and contamination levels can differ widely between samples. These factors make cardarine a regulatory and public health concern rather than a conventional prescription drug.
Cardarine is a common name for GW501516, a synthetic compound first described in the 1990s as a selective agonist of the peroxisome proliferator-activated receptor delta. It was studied in preclinical models for metabolic and cardiovascular conditions, but it has not been approved as a medicine in the United States, Europe, or other major jurisdictions. Retail products labeled as cardarine are generally research chemicals or supplements, not pharmaceutical formulations. Because human safety and efficacy data remain limited, regulatory agencies treat it as an unapproved substance rather than a therapeutic product.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | GW501516; GW-1516; endurobol | GW501516 is the research code |
| Drug class | PPARδ agonist | Not a selective androgen receptor modulator |
| Molecular formula | C21H18F3NO3S2 | Established chemical formula |
| Molar mass | 453.5 g/mol | Calculated from the formula |
| Regulatory status | Prohibited in sport; not approved as medicine | Status varies by country |
Cardarine is explicitly prohibited by the World Anti-Doping Agency under the class of PPARδ agonists. Its presence in urine or blood samples can be detected using mass spectrometry-based methods, often liquid chromatography-tandem mass spectrometry. Athletes who test positive may face sanctions, including bans from competition. The compound is also regulated as a prescription-only or unapproved drug in many countries. Enforcement varies by jurisdiction, and some regions treat it as a controlled substance. Online sales may occur despite these restrictions, creating quality and legal risks.
Laboratory detection of cardarine typically involves sample preparation followed by chromatographic separation and mass spectrometric identification. Urine is the most common matrix for anti-doping tests, though blood and hair have also been explored. Methods can target the parent compound or its metabolites, depending on the expected window of detection. Reference standards are required for accurate quantification. Matrix effects and dilution can influence results, so laboratories use internal standards and validation protocols. The exact detection window varies with dose, route, and individual metabolism.
Anti-doping laboratories detect GW501516 and its metabolites using liquid chromatography-tandem mass spectrometry. Urine is the most common matrix, though blood and dried blood spots may also be used in some programs. Detection depends on factors such as dose, timing, metabolism, and the sensitivity of the assay. Published methods describe limits of detection in the low nanogram per milliliter range for related compounds. Exact detection windows are not fixed for all situations and remain an area of ongoing study.
Products sold as cardarine have been found to contain incorrect compounds, variable amounts, or no active ingredient at all. Independent testing is required to verify identity and purity. Common analytical approaches include high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance for structural confirmation. These methods can distinguish GW501516 from related PPAR agonists and from unrelated steroids. For regulators and researchers, such verification is central to interpreting both biological results and adverse event reports.
Cardarine is prohibited in competitive sport under the World Anti-Doping Agency code, where it is classified as a metabolic modulator. It is not approved as a prescription medicine in the United States, European Union, or other major markets. Regulatory action has focused on its presence in sports and in products marketed as research chemicals. Because it has no accepted medical indication, supply is often unregulated. This status creates legal and safety uncertainties for anyone who encounters the substance.
Laboratory studies indicate that GW501516 activates PPARδ, a nuclear receptor involved in fatty acid oxidation and energy metabolism. In rodent experiments, treated animals often showed increased endurance and reduced fat mass. These effects were observed under controlled conditions and do not establish safe or effective use in humans. The exact dose-response relationship in humans remains poorly characterized. Species differences in metabolism can affect how results translate across animals and people.
Safety concerns emerged from long-term animal studies. In rodents given the compound for extended periods, researchers found an increased incidence of certain cancers, including liver and bladder tumors. These findings contributed to the discontinuation of clinical development. Whether similar risks apply to short-term or low-level exposure in humans is not established, and controlled human safety data are limited. The relevance of high-dose rodent carcinogenicity findings to human use remains a subject of debate.
Human trials of GW501516 were small and short in duration. They examined lipid levels, glucose handling, and other metabolic markers, but the programs were halted after the animal cancer findings. No approved therapeutic product exists, and published human data are insufficient for establishing long-term safety. Reports of use for athletic performance come mainly from non-clinical settings and cannot be verified through controlled trials. Independent testing of products sold as cardarine has found inconsistent purity and labeling.
=== Multiple risk factor theory === Another theory is that there may be shared risk factors that can lead to both substance use and mental illness. Mueser hypothesizes that these may include factors such as social isolation, poverty, lack of structured daily activity, lack of adult role responsibility, living in areas with high drug availability, and association with people who already misuse drugs. Other evidence suggests that traumatic life events, such as sexual abuse, are associated with the development of psychiatric problems and substance use.
=== Megaloblastic anemia === Neutrophil hypersegmentation is one of the earliest, most sensitive and specific signs of megaloblastic anemia (mainly caused by hypovitaminosis of vitamin B12 & folic acid). Nuclear hypersegmentation of DNA in neutrophils strongly suggests megaloblastosis when associated with macro-ovalocytosis. If megaloblastosis is suspected, a formal lobe count/neutrophil (i.e. lobe index) above 3.5% can be obtained. Hypersegmentation persists for an average of 14 days after institution of specific therapy.
=== Preclinical === Dimethyltryptamine (DMT) – non-selective serotonin receptor agonist and psychedelic hallucinogen EX-14280 – fatty acid amide hydrolase (FAAH) inhibitor EX-14663 – fatty acid amide hydrolase (FAAH) inhibitor PSYLO-3001 (Psylo-3001) – non-selective serotonin receptor agonist and psychedelic hallucinogen Research programme: CNS disorders and substance-related disorders therapeutics - Kinoxis Therapeutics — oxytocin receptor modulators
It is theoretically a sound hypothesis that the spermatogenesis can be increased by indirectly stimulating FSH and LH secretions from the pituitary gland. However, for this to fructify, it requires the use of testosterone antagonist to nullify the negative feedback effect of circulating testosterone on the release of FSH and LH, thus augmenting the secretion of testosterone and spermatogenesis. Unfortunately, a testosterone antagonist will be unacceptable to males, as it may reduce secondary sexual functions including erection and ejaculation that is vital for the successful fertilization. However, while bicalutamide does not appear to adversely influence testicular spermatogenesis, and healthy sperm can be produced within the testes during bicalutamide monotherapy, AR antagonists may be able to interfere with male fertility via interference with androgen signaling beyond the testes. The maturation as well as transport of sperm occurs not only in the testes but also outside of the testes in the epididymides and vas deferens, and these processes in these tissues are dependent on AR signaling similarly to testicular spermatogenesis. However, whereas androgen levels are extremely high in the testes, this is not true in the epididymides and vas deferens. As androgen levels are relatively low in these tissues, at least compared to the testes, bicalutamide may be able to block AR signaling in these parts of the body to an extent that is sufficient to interfere with male fertility.
Sources: en.wikipedia.org
== Training == Proprioception is what allows someone to learn to walk in complete darkness without losing balance. During the learning of any new skill, sport, or art, it is usually necessary to become familiar with some proprioceptive tasks specific to that activity. Without the appropriate integration of proprioceptive input, an artist would not be able to brush paint onto a canvas without looking at the hand as it moved the brush over the canvas; it would be impossible to drive an automobile because a motorist would not be able to steer or use the pedals while looking at the road ahead; a person could not touch type or perform ballet; and people would not even be able to walk without watching where they put their feet. Oliver Sacks reported the case of a young woman who lost her proprioception due to a viral infection of her spinal cord. At first she could not move properly at all or even control her tone of voice (as voice modulation is primarily proprioceptive). Later she relearned by using her sight (watching her feet) and inner ear only for movement while using hearing to judge voice modulation. She eventually acquired a stiff and slow movement and nearly normal speech, which is believed to be the best possible in the absence of this sense. She could not judge effort involved in picking up objects and would grip them painfully to be sure she did not drop them.
== Diagnosis == The symptoms of a metabolic myopathy can be easily confused with the symptoms of another disease. As genetic sequencing research progresses, a non-invasive neuromuscular panel DNA test can help make a diagnosis. Whole genome sequencing is required in more complex cases. If the DNA test is inconclusive (negative or VUS), then a muscle biopsy is necessary for an accurate diagnosis. In mitochondrial myopathies involving a single mtDNA deletion, DNA would have to be tested from affected muscle tissue rather than saliva or blood as unaffected tissues would show normal or near normal levels of mtDNA. A blood test for creatine kinase (CK) can be done under normal circumstances to test for signs of tissue breakdown, or with an added cardio portion that can indicate if muscle breakdown is occurring. In metabolic myopathies, baseline CK is either normal or elevated. An electromyography (EMG) test is sometimes taken in order to rule out other disorders if the cause of fatigue is unknown. In metabolic myopathies, the EMG is either normal or myopathic, but spontaneous activity is usually absent. An exercise stress test can be used to determine an inappropriate rapid heart rate (sinus tachycardia) response to exercise, which is seen in GSD-V, other glycogenoses, and mitochondrial myopathies. A 12 Minutes Walk Test (12MWT) can also be used to determine "second wind" which is also seen in McArdle disease (GSD-V) and phosphoglucomutase deficiency (PGM1-CDG/CDG1T/GSD-XIV).
Interpreting this as a sign that Smith intended to declare independence if a majority backed it in the referendum, Wilson wrote a stiff letter to Smith on 25 October, warning him of the consequences of UDI, and demanding "a categorical assurance forthwith that no attempt at a unilateral declaration of independence on your part will be made". Smith expressed confusion as to what he had done to provoke this, and ignored it. When the indaba ended on 26 October, the chiefs and headmen returned a unanimous decision to support the government's stand for independence under the 1961 constitution, attesting in their report that "people who live far away do not understand the problems of our country". This verdict was rejected by the nationalist movement on the grounds that the chiefs received governmental salaries; the chiefs countered that the black MPs in parliamentary opposition also received such salaries, but still opposed the government. Malvern, who was becoming perturbed by the RF's actions, dismissed the indaba as a "swindle", asserting that the chiefs no longer had any real power; the British simply ignored the whole exercise. On 27 October, Wilson released a firm statement regarding Britain's intended response to UDI, warning that Rhodesia's economic and political ties with Britain, the Commonwealth and most of the world would be immediately severed amid a campaign of sanctions if Smith's government went ahead with UDI.
Sources: en.wikipedia.org
== Development == Half-Life 2: Deathmatch was started as a test while Half-Life 2 was being developed. Designer Adrian Finol wanted to know what it was like to use the gravity gun in a multiplayer setting, creating a build that showcased Half-Life 2 multiplayer. Scott Dalton created a map and the two played in the office, and Gabe Newell asked to be shown the product. Finol pushed for multiplayer so mod makers could access the tools to create their own levels. Upon the release and subsequent critical reception of Half-Life 2, reviewers expressed disappointment with the game's lack of multiplayer. Two weeks after the initial release of Half-Life 2, Valve revealed and released Half-Life 2: Deathmatch on Steam. Deathmatch was released simultaneously with the Source SDK as a means of promoting game modifications built upon the platform. Post-release, the game was supported with new maps from Valve as well as updates to the game and its engine. Valve's The Orange Box originally did not include Half-Life 2: Deathmatch, however, the game was upgraded to use the Orange Box version of the Source engine in September 2010. Valve announced a free promotional offer on January 10, 2008, which allowed NVIDIA graphics card users to download and play Half-Life 2: Deathmatch along with Portal: First Slice, Half-Life 2: Lost Coast, and Peggle Extreme. In September 2010, the game was released via Steam for OS X. A Linux version came more than two years later, in March 2013.
== Bodybuilding titles == 1984 Mr Birmingham Novice, 1st 1985 World Games, 7th Heavyweights 1986 British Championships, 1st Heavyweight 1988 British Championships, 1st Heavyweight and overall 1990 Night of Champions, 2nd 1991 Night of Champions, 1st 1991 Mr. Olympia, 2nd 1991 English Grand Prix, 1st 1992 Mr. Olympia, 1st 1992 English Grand Prix, 1st 1993 Mr. Olympia, 1st 1994 Mr. Olympia, 1st 1994 Mr. Worldwide, 1st 1994 Spanish Grand Prix, 1st 1994 German Grand Prix, 1st 1994 English Grand Prix, 1st 1995 Mr. Olympia, 1st 1996 Mr. Olympia, 1st 1996 Spanish Grand Prix, 1st 1996 German Grand Prix, 1st 1996 English Grand Prix, 1st 1997 Mr. Olympia, 1st
If a lich's corporeal body is destroyed, the portion of its soul that remained in the body does not pass on to the afterlife; rather, it persists in a non-corporeal form capable of being reconstituted or resurrected. However, if all of a lich's soul-artifacts are destroyed, its only remaining anchor to the material world becomes its corporeal body—meaning that its destruction would result in permanent death.
Pyrite.Virtual Museum of Mineralogy. Universidad de Zaragoza, Spain Educational article about the famous pyrite crystals from the Navajun Mine How Minerals Form and Change "Pyrite oxidation under room conditions". Poliakoff, Martyn (2009). "Fool's Gold". The Periodic Table of Videos. University of Nottingham.
Sources: en.wikipedia.org
No. Cardarine is GW501516, a PPARδ agonist, while SARMs act on androgen receptors. The two classes are often grouped in informal discussions despite different mechanisms.
No. It has no approved medical indication in any country. Regulatory agencies have not cleared it for treatment or prevention of any condition.
Early clinical work stopped after rodent carcinogenicity findings. Those animal results raised concerns about long-term human risk, although direct human evidence is lacking. The human relevance of the tumors remains an open scientific question.
No. Major drug regulators have not approved GW501516 for treating any medical condition. Products sold as cardarine are typically unapproved research chemicals or supplements, so their contents and safety are not assured.