Limited · human
This study developed and validated a unified chromatographic-mass spectrometric (LC-MS) method for detecting a broad range of prohibited peptide drugs (molecular mass 2–10 kDa) in doping control urine samples. The target analytes spanned five categories: insulins (human and animal-derived, including several analogues and a metabolite), growth hormone-releasing hormones (GHRHs) and their metabolites, insulin-like growth factors (IGF variants), synacthen, gonadorelin, and mechano growth factors. A key goal was simplifying sample preparation by consolidating what are traditionally separate, complex analytical workflows into a single procedure, controlled by five internal standards—one per peptide category. The method was validated as an initial testing procedure and shown to meet nearly all World Anti-Doping Agency (WADA) Minimum Required Performance Levels (MRPLs). As a proof of principle, the method was applied to authentic post-administration urine samples from human subjects dosed with insulins and gonadorelin, demonstrating real-world detection capability. Limitations include that human subject data are limited to proof-of-concept post-administration samples rather than a controlled efficacy or pharmacological trial, and the study's primary focus is analytical method development rather than clinical outcomes.
Journal of mass spectrometry : JMS · Jan 2024DOI ↗ Limited · human
This prospective, open-label, randomized pilot trial (NCT04487444) evaluated the preliminary efficacy and safety of thymalfasin (synthetic Thymosin-α-1, or Tα1) compared with standard of care in 49 hospitalized COVID-19 patients presenting with both hypoxemia and lymphocytopenia. The primary clinical outcome—rate of clinical recovery—was numerically higher in treated patients receiving either low-flow or high-flow baseline oxygen support, but neither difference reached statistical significance (subdistribution hazard ratios of 1.48 and 1.28, respectively, with wide confidence intervals crossing 1.0). A notable immunological finding was that treated patients on baseline low-flow oxygen had, on average, 3.84 times more CD4+ T cells on day 5 compared with day 1, versus controls (P = .01), suggesting faster T-cell reconstitution. Nine serious adverse events occurred in the treatment group but were adjudicated as unrelated to Tα1. Key limitations include the small sample size (n=49), open-label design (no blinding), and lack of statistical power to draw definitive efficacy conclusions. The authors suggest Tα1 may have a role in managing COVID-19-related immunosuppression, but larger trials are needed to confirm these preliminary findings.
The Journal of infectious diseases · Jan 2023DOI ↗ Limited · human
This case report tracked a single 25-year-old recreationally active male who self-administered LGD-4033 (a selective androgen receptor modulator) and MK-677 (a growth hormone secretagogue) daily for five weeks. Blood work and body composition (via DXA) were collected before, during, and after the cycle, while muscular strength and skeletal muscle androgen-related biomarkers were assessed during the cycle and compared cross-sectionally against data from non-using trained males. The study observed increases in total body mass, lean mass, and fat mass during the cycle, alongside adverse changes in bone mineral content and density, serum lipids (notably a 40% rise in LDL and a 36% drop in HDL), and liver enzymes (ALT rose over 200%). Total and free testosterone and sex hormone-binding globulin fell markedly during the cycle. Most biomarkers returned toward baseline post-cycle, though total cholesterol, LDL, total fat mass, and bone area did not fully recover. Follicle-stimulating hormone remained below clinical reference ranges even post-cycle. Compared with non-users, the subject showed higher intramuscular testosterone and dihydrotestosterone but lower androgen receptor content, alongside greater strength. Key limitations include the single-subject design, lack of a control group, and reliance on cross-sectional comparisons for intramuscular and strength data, making causal inferences unreliable.
Experimental physiology · Nov 2022DOI ↗ Limited · human
This study investigated a method for detecting a broad range of peptide-based doping agents (molecular mass 2–10 kDa) in blood samples collected for anti-doping control purposes. Researchers developed a simplified, generic sample preparation workflow using mixed-mode solid-phase extraction (SPE), coupled with liquid chromatography and high-resolution mass spectrometry (HRMS; resolution >100,000 FWHM) as an initial testing procedure. The target analytes included multiple insulin variants (human and synthetic analogues such as lispro, aspart, glulisine, detemir, glargine, and others), growth hormone–releasing hormones (sermorelin, CJC-1295, tesamorelin), insulin-like growth factors (Long-R3-IGF-I, R3-IGF-I, Des1-3-IGF-I), and mechano growth factors. The study demonstrated that the method met WADA's Technical Document 2022 (TD2022 MRPL) requirements for minimum required performance levels. Proof-of-principle was shown using real post-administration blood samples from subjects treated with synthetic insulin analogues. A key advantage noted was that blood, unlike urine, contains intact peptide hormones at relatively higher concentrations, simplifying detection. Limitations include the study's primarily analytical/methodological scope and the small number of post-administration samples used for validation.
Analytical science advances · Aug 2022DOI ↗ Limited · human
This paper presents a case report of a 27-year-old male with no relevant medical history who attended an emergency department two hours after self-administering Melanotan II (also marketed as a "Barbie drug") subcutaneously. Melanotan II is a synthetic analogue of alpha-melanocyte-stimulating hormone (α-MSH) that stimulates eumelanin production to induce skin pigmentation without sun exposure. It is readily available for purchase online and in gyms, despite not being approved for clinical use. Following self-administration, the patient developed sympathomimetic symptoms requiring treatment with lorazepam, supplemental potassium, and intravenous fluid resuscitation. The authors also note that prior research has associated Melanotan II use with the development of new pigmented and dysplastic naevi, raising additional dermatological safety concerns. The paper concludes that despite its easy accessibility, Melanotan II carries real and potentially serious risks. Key limitations include its single-patient case design, which precludes generalization about incidence or severity of adverse effects across the broader population of users.
Nederlands tijdschrift voor geneeskunde · May 2022Source ↗ Limited · human
This study compared the growth hormone (GH) response elicited by a single oral dose of LUM-201 (ibutamoren/MK-0677), a GH secretagogue receptor agonist, to responses from standard diagnostic GH stimulation tests (arginine, glucagon, clonidine, L-dopa, and insulin-induced hypoglycemia) in 68 pediatric subjects enrolled in a pediatric growth hormone deficiency (PGHD) clinical trial. The study found that LUM-201 produced significantly greater GH responses than the conventional secretagogues, with median peak GH of 15.0 ng/mL versus 5.5 ng/mL for standard tests (p-value not fully captured in abstract but reported as statistically significant). Notably, the larger GH responses to LUM-201 were most pronounced in subjects who also showed higher peak GH responses to conventional testing, suggesting a functional somatotroph reserve may be required. The authors concluded that LUM-201 may represent a potential oral treatment alternative to injectable recombinant human GH (rhGH) in a subset of PGHD patients who demonstrate adequate acute GH responses to LUM-201. Limitations include the lack of a placebo-controlled design, relatively small sample size, and the single-dose comparison design which does not assess long-term growth outcomes.
Hormone research in paediatrics · Mar 2022DOI ↗ Limited · human
This case report by Mallory, Lopategui, and Cordon (Sexual Medicine, 2021) describes a single patient who developed acute ischemic priapism following subcutaneous self-administration of Melanotan II, a synthetic melanocortin analog that is illicitly sold online and used in unlicensed clinics as a sunless tanning agent and sexual stimulant. The authors note that Melanotan II has also been investigated as a potential treatment for erectile dysfunction. In this case, standard first-line management — including cavernosal aspiration, irrigation, and intracavernous phenylephrine injection — failed to achieve detumescence. The patient ultimately required surgical intervention via penoscrotal decompression, which the authors describe as a promising technique for refractory ischemic priapism. The report notes that priapism associated with Melanotan II had only been documented twice previously in the literature. The authors conclude that priapism should be recognized as a possible adverse effect of Melanotan II and that future therapeutic investigations and clinical guidelines should account for this risk. Key limitations include the inherent constraints of a single case report: findings cannot be generalized, causality cannot be definitively established, and no controlled comparison is possible.
Sexual medicine · Jan 2021DOI ↗ Limited · human
This paper presents a case report combined with a literature review examining a possible association between Melanotan II (MTII) — a non-selective melanocortin-receptor agonist commonly used illicitly for skin tanning, penile erection, and sexual stimulation — and renal infarction. The authors describe a patient who experienced renal infarction most likely attributed to MTII use. Renal infarction, an uncommon and potentially life-threatening condition caused by acute disruption of renal blood flow, is noted to be frequently misdiagnosed or diagnosed late. The paper reviews prior literature documenting MTII-associated rhabdomyolysis and renal failure, and proposes two potential mechanisms of renal injury: a thrombotic pharmacological effect and possible direct toxic effects on renal parenchyma. Limitations are significant: evidence rests on a single case and a narrative review of prior case-level reports, meaning causality cannot be formally established. No controlled data are available, and the condition's rarity makes systematic study difficult. The authors conclude that MTII's thrombotic and potentially nephrotoxic properties warrant clinical awareness, particularly given the compound's widespread unregulated use.
CEN case reports · Jan 2020DOI ↗ Limited · human
This study developed and validated an analytical method for detecting a broad panel of 18 performance-enhancing peptides (molecular weight <2 kDa) in human urine, as defined by the World Anti-Doping Agency (WADA) prohibited list. The method uses direct urine injection—bypassing complex sample preparation—coupled with liquid chromatography and ion mobility time-of-flight mass spectrometry (IM-TOFMS). The researchers reported limits of detection (LOD) ranging from 50 to 500 pg/mL, well below WADA's minimum required performance level of 2 ng/mL. The method demonstrated acceptable precision (imprecision <20%) and linearity across a 0–10 ng/mL working range. Stability testing identified –20°C as the appropriate storage temperature for urine samples. As a proof-of-concept, the method was applied to real elimination study urine samples from individuals who had administered GHRP-2, GHRP-6, or LHRH, successfully detecting these compounds. Key limitations include the small number of human subjects used in the elimination studies, which were primarily intended to demonstrate analytical feasibility rather than investigate pharmacokinetics or clinical effects. The study is a methodological/analytical validation paper focused on anti-doping screening, not a clinical or therapeutic investigation.
Journal of separation science · Dec 2015DOI ↗