N-ethyl Tadalafil: One Molecule, Five Names, and a Search That Misses Half the Literature

Search the analytical literature for N-ethyl Tadalafil and you will find perhaps fifteen papers. Search it for homotadalafil and you will find a different set. The two searches describe one compound.

PubChem resolves both names to a single record, CID 101494198, with one CAS number and one InChIKey. The systematic name settles it: 2-ethyl on the piperazinedione ring. Anyone building a reference collection or a literature review from a single name is working from half the record.

Kimera supplies N-ethyl Tadalafil as an analytical reference standard and for structure-activity relationship work. It is research material, not a pharmaceutical, and not a substitute for any approved product. Tadalafil itself is an approved pharmaceutical and is not in this catalogue.

All information here describes laboratory research findings. This material is supplied for research use only and is not for human or veterinary use.

What N-ethyl Tadalafil is

Take tadalafil and replace the methyl group on the piperazinedione nitrogen with an ethyl group. That single substitution adds one CH2 unit, moving the mass from 389.4 to 403.4.

Identity and physical data

The names it travels under

The same PubChem record lists all of the following for this one compound:

Only two of those five state where the addition sits. That is the practical problem, and it is not a trivial one.

The homo prefix does not locate anything

“Nor” and “homo” are complementary prefixes. Nor means a CH2 removed, homo means a CH2 added. Neither says where.

Why that matters for this scaffold

The tadalafil scaffold has several positions that could in principle accept a methyl. A name built on the homo prefix therefore describes a mass change rather than a structure. A name built on N-ethyl describes a structure.

In practice the literature uses homotadalafil for this compound specifically, and the PubChem record reflects that convention. Convention is not the same as specification. A paper reporting homotadalafil without a structure or an InChIKey has not told you which position carries the extra carbon.

The check that settles it

Read the systematic name or the InChIKey rather than the trivial name. For N-ethyl Tadalafil the systematic name contains 2-ethyl, and the first InChIKey block is QGNIMKVVHAXCSK. Either one is unambiguous where the trivial names are not.

The plus-fourteen problem

A 14 Da mass difference is the most common spacing in all of organic mass spectrometry, because it is one CH2. That makes it the least informative shift a screen can observe.

What a mass screen actually establishes

Finding a peak at 403.4 where tadalafil sits at 389.4 tells you a methylene has been added somewhere. It does not tell you where. Chain extension at the piperazinedione nitrogen produces that shift, and so would methylation elsewhere on the scaffold.

The family makes this concrete. Reported analogs of this scaffold span at least eight different substituents at the same nitrogen, each with its own mass [1][2][3][4][5][6][7]. Several sit close enough together that precursor mass alone cannot separate them from an isomer.

Why the usual detectors do not rescue it

Two independent groups have reported that ultraviolet spectra of analogs in this family are almost identical to tadalafil [5][7]. One added that tandem mass fragmentation was highly similar below 300 m/z [7]. The chromophore is the benzodioxole and indole system, and substitution at the distant nitrogen barely perturbs it.

So a diode array trace shows one shape, and low-mass fragments show one core. The distinguishing information sits entirely in the precursor mass and in the fragments above the substituent, which is a narrow evidence base for an identification.

What the survey literature reports

N-ethyl Tadalafil and its relatives appear in the analytical record because regulators screen consumer products for undeclared compounds.

The candy, the honey and the tablet

A 2021 study isolated pharmaceutical ingredients from three products bought online: a honey preparation and a tablet containing tadalafil, and a candy containing nortadalafil and homotadalafil [8]. That homotadalafil is the compound described here.

Every isolate matched the 6R,12aR standard by circular dichroism. So the material found in real samples carries the same configuration as the catalogue reference standard.

Base rates from screening surveys

A 2018 survey of tonic liquors screened for 86 phosphodiesterase type 5 inhibitors and found undeclared compounds in 14.3 percent of samples [9]. A 2023 study using thin layer chromatography with mass spectrometric confirmation found sildenafil, tadalafil or both in 73.3 percent of the products it tested, all of them labelled natural [10].

Those percentages come from products already under suspicion. They establish that the analysis is worth funding, not a population prevalence.

Immunoassay picks up the group

A 2022 study raised antibodies against a computationally designed hapten and built an indirect competitive ELISA [11]. It detected five compounds of this family at once, with limits of detection from 0.004 to 0.396 ng/mL, correlating with HPLC-MS/MS at R of 0.9955.

That approach screens groups rather than compounds. It flags the scaffold and leaves identification to a confirmatory method.

Stereochemistry, and what a purity assay cannot see

The InChIKey for N-ethyl Tadalafil ends VGOFRKELSA rather than UHFFFAOYSA. A defined stereo block means the record describes one specific stereoisomer.

Two stereocentres, four possible isomers

The scaffold carries stereocentres at positions 6 and 12a. The catalogue material is the (6R,12aR) form, matching what analysts report from real samples [8].

A routine achiral purity assay reports how much non-target material is present. It reports nothing about which stereoisomer the target is. Those are different questions answered by different methods.

The clearest published demonstration

A 2019 study isolated a stereoisomer of a related analog and could not place it by mass [12]. High resolution mass spectrometry gave the same precursor ion within 2 ppm as two trans isomers, retention times sat very close, and fragmentation matched.

Resolution required a chiral column, then comparison of ellipticity and optical rotation against homologous compounds, then NOESY. Three orthogonal techniques, none of them mass spectrometry.

What to request

Where configuration matters to the work, ask for a chiral method with its chromatogram, or a circular dichroism spectrum measured against a standard. A certificate reporting purity by an achiral method is consistent with any stereoisomeric composition. Batch documentation for catalogue material sits in the certificate of analysis database.

Searching the literature without missing half of it

This section is the practical payoff of the naming problem.

Query on every name

A search for N-ethyl Tadalafil alone will miss papers indexed under homotadalafil, and the reverse holds. Include both, plus the CAS number 1609405-34-6, which is the most reliable single query term because it does not vary with author preference.

Beware auto-mapping

Database term mapping can silently widen or narrow a query. In this compound family, searching a trivial name can expand to the parent drug concept and return thousands of irrelevant records. Restricting to title and abstract fields defeats that expansion where it happens.

Check the query translation your database reports back, rather than the result count. A large number is not evidence of a large literature.

Read the structure, not the name

Where a paper reports a compound by trivial name only, treat the identification as provisional until a structure, systematic name, InChIKey or CAS appears. This family has generated enough near-identical names that the trivial name alone carries real ambiguity.

How this literature began

The analytical record on this scaffold has a clear starting point, and knowing it explains why the field is shaped as it is.

The 2006 paper

The earliest report isolated a tadalafil analog alongside hydroxyhomosildenafil from a herbal product (DOI). Its authors identified the compound by LC-UV, high resolution mass spectrometry, tandem mass spectrometry, infrared and NMR, and closed with a recommendation: the compound should be included as a target when screening for adulterants [13].

That recommendation set the pattern every subsequent paper follows. Isolate, elucidate, name, then propose the compound for inclusion on screening lists. Nineteen years of literature run on that template.

The geographic spread

A 2015 report from Argentina identified aminotadalafil in a supplement and described itself as the first such study in Latin America [14]. Its authors noted that unapproved analogs carry an unquantified risk precisely because nobody has assessed them.

Reports since have come from Singapore, Korea, Taiwan, Japan, China and Romania [1][3][6][8][10]. The compounds are the same and the laboratories are national regulators. That is what a global screening effort looks like when nobody coordinates it.

Why N-ethyl Tadalafil sits in the middle of it

Reference standards exist because confirmation requires them. A regulator who isolates an unknown can elucidate its structure, but confirming that structure against an authentic sample needs the sample to exist. For N-ethyl Tadalafil that sample is a catalogue item, which is the whole legitimate function of the material.

In biological matrix, the parent may be absent

Product analysis and biological analysis are different problems, and a method built for one will not serve the other.

The metabolite finding

A 2025 forensic method quantified four phosphodiesterase type 5 inhibitors and twelve metabolites in rat plasma (DOI). Its most useful result for method design is a negative one.

Desmethyltadalafil and methyl-desmethyltadalafil were not detected in plasma at all [15]. Their glucuronide conjugates were, and tandem mass spectrometry characterised them.

What that implies

A screen built to find parent compounds in a biological sample can return clean while the compound was present. The signal moved to a conjugate the method was not looking for.

Any protocol analysing biological matrix rather than product powder should include the expected phase two conjugates, or should hydrolyse before analysis. Building the method around the parent alone is the error the 2025 paper documents.

Matrix effects run in the same direction

The same study reported matrix factors from 2.1 to 20.4 percent and recoveries above 75.5 percent across sixteen analytes [15]. Those numbers are acceptable and they are not negligible, which is the point. Establish them for the matrix in hand rather than importing them from a paper.

Physicochemical properties and handling

The tetracyclic core is rigid and largely planar, which keeps aqueous solubility low. Prepare concentrated stocks in DMSO and dilute into buffer immediately before use.

Protect the configuration

Kimera ships a single defined stereoisomer, and that configuration is the property the material exists to provide. Avoid strongly basic conditions and prolonged heating in solution, since the position alpha to the ring carbonyl is where epimerisation would occur.

Verify configuration rather than assuming a certificate still describes an aliquot after months of storage. For a compound bought specifically for its stereochemistry, that check is the point.

N-ethyl Tadalafil among the phosphodiesterase inhibitors

The catalogue category holds six compounds across two unrelated scaffolds.

The tadalafil family is a homologous series

Read that first column downward and the pattern is a methylene ladder: minus one CH2, the parent, plus one, plus two. A homologous series of this kind is the classic hard case for mass-based identification, because each step is the same 14 Da.

Retention behaviour shifts predictably along such a series, which makes chromatography more useful here than usual. Elution order across the series is worth establishing once and keeping.

Further reading sits in the PDE5 inhibitor research library, and the reference standard ships against batch documentation.

Building a reference set for the homologous series

A laboratory covering this family faces a purchasing question before it faces an analytical one.

Buy the ladder, not the rungs you expect

The tadalafil family forms a methylene series, and retention shifts predictably along it. Holding the parent, the nor compound and N-ethyl Tadalafil establishes three points on that line. A fourth at plus 28 fixes the slope well enough to predict where an unknown homolog should elute.

That prediction is the practical value. An unknown falling on the line is probably a homolog; one falling off it probably is not. Neither conclusion is available from a single standard.

Establish elution order once

Run the series together under the intended conditions and record the order. It rarely changes across similar reversed-phase methods, and having it written down converts an unexpected peak from a mystery into a position on a known scale.

Keep the chromatogram. The next analyst will otherwise repeat the work, and reference standards are consumed each time.

Cross-check every standard on receipt

Suppliers of research chemicals vary, and the naming ambiguity described above reaches into catalogues as well as papers. Confirm identity by mass and by NMR on arrival rather than trusting the label, particularly where a compound has multiple accepted names.

For N-ethyl Tadalafil the fastest check is the ethyl signal: a triplet and a quartet with the integration of five protons, absent in the nor compound and different in the isopropyl analog.

Record what you cannot resolve

Where a method cannot separate two candidates, say so in the report rather than choosing the likelier one. An identification qualified as “consistent with” is more useful downstream than a confident assignment that later needs retracting.

Open questions and how to read this literature

There is essentially no pharmacology

Papers naming this compound are analytical and forensic almost without exception. Isolation, structure elucidation, method development, survey. Statements about what it does at its target are read across from the parent scaffold rather than measured on the compound.

The 2021 configuration study is careful about this. It cites a report that the 6R,12aR isomers of tadalafil carry the most potent inhibitory activity, then suggests a comparable strength for the analogs [8]. Suggests is the operative word, and read-across is a hypothesis.

The naming problem is unresolved and spreading

Every new analog in this family arrives with a trivial name coined by its discoverers. Some name the substituent, some use homo or nor, some use a laboratory code. No convention governs the choice.

That is a literature problem rather than a chemistry problem, and it grows with each new report. A structure-searchable database entry is the only durable fix.

Quantitative reference data is thin

Authentic standards exist for few of the substituted analogs, and published quantitative NMR data is thinner still. A laboratory confirming an identification against a compound nobody sells has to synthesise it or report the identification as tentative.

What would help

Consistent reporting of InChIKeys alongside trivial names would close most of the ambiguity at no cost. It is already standard practice in some journals in this field and absent in others.

Frequently asked questions

Is N-ethyl Tadalafil the same as homotadalafil?

Yes. PubChem resolves both names to CID 101494198, with CAS 1609405-34-6 and a single InChIKey. The systematic name specifies 2-ethyl.

Why do two names exist for one compound?

They come from different naming systems. One names the substituent and its position, the other records that a CH2 was added without saying where. Both entered the literature independently.

How does N-ethyl Tadalafil differ from tadalafil structurally?

By one CH2. The methyl on the piperazinedione nitrogen becomes an ethyl, moving mass from 389.4 to 403.4 [8].

Can a mass screen identify it?

Not on its own. A 14 Da shift is one methylene and locates nothing, and analogs in this family share both the ultraviolet spectrum and the low-mass fragments of tadalafil [5][7].

Does it need a chiral purity method?

If the work depends on configuration, yes. Two stereocentres mean four possible stereoisomers, and no achiral assay distinguishes them [12].

Which name should a purchase order use?

The CAS number, 1609405-34-6. It does not vary with author or supplier preference, where the trivial names do. Quote the name alongside it for readability.

What is the quickest identity check on receipt?

Proton NMR. The ethyl group gives a triplet and a quartet integrating for five protons, which distinguishes N-ethyl Tadalafil from the nor compound and from the larger alkyl analogs in one spectrum.

Is this a generic of an approved drug?

No. A generic contains the same active ingredient as the brand. This is a structurally different molecule with its own formula, CAS number and regulatory status, supplied as a research reference material.

References

1. Xu Y, Kee CL, Ge X, et al. Isolation and characterization of a tadalafil analogue, N-cyclopentyl nortadalafil in health supplement. J Pharm Biomed Anal. 2015;118:235-241. PubMed DOI
2. Huang YC, Lee HC, Lin YL, et al. Separation and identification of a novel tadalafil analogue adulterant in a dietary supplement. Food Addit Contam Part A. 2016;33(2):179-85. PubMed DOI
3. Park HN, Lee JH, Park SK, et al. Identification of a new tadalafil analogue in commercial dietary supplements: isopropylnortadalafil. Food Addit Contam Part A. 2017;34(2):162-169. PubMed DOI
4. Lee JH, Park HN, Ganganna B, et al. Isolation and structural elucidation of a new tadalafil analogue in health supplements: bisprenortadalafil. Food Addit Contam Part A. 2016;33(6):945-52. PubMed DOI
5. Dong PZ, Liu XP, Zhang L, et al. Isolation and characterisation of N-benzyl tadalafil as a novel adulterant in a coffee-based dietary supplement. Food Addit Contam Part A. 2020;37(12):2033-2039. PubMed DOI
6. Lee HC, Lin YL, Huang YC, et al. Identification of a new tadalafil analogue, N-3-hydroxypropylnortadalafil, in a supplement product. J Pharm Biomed Anal. 2018;158:257-261. PubMed DOI
7. Liu J, Sun J, Wei H, et al. Isolation and characterization of a novel tadalafil analogue adulterant, N-cyclohexyl nortadalafil, in a dietary supplement. J Pharm Biomed Anal. 2023;227:115144. PubMed DOI
8. Fukiwake T, Yamazaki M, Takahashi K, et al. The Configuration of Tadalafil and Tadalafil Analogues Found in Dietary Supplements. Shokuhin Eiseigaku Zasshi. 2021;62(2):65-72. PubMed DOI
9. Ding B, Wang Z, Xie J, et al. Phosphodiesterase-5 inhibitors in Chinese tonic liquors by liquid chromatography coupled with quadrupole time of flight mass spectrometry. Food Addit Contam Part B. 2018;11(3):214-222. PubMed DOI
10. Gheorghiu ORC, Ciobanu AM, Guțu CM, et al. Determination of Phosphodiesterase Type-5 Inhibitors (PDE-5) in Dietary Supplements. Molecules. 2023;28(10):4116. PubMed DOI
11. Yang JY, Xie MC, Tan XC, et al. Improved molecular softness of tadalafil hapten enhancing antibody performance in immunoassay. J Food Sci. 2022;87(3):1342-1354. PubMed DOI
12. Kee CL, Chin LC, Cheah NP, et al. Elucidation of the absolute configuration of a tadalafil analogue found as adulterant in a health supplement by mass spectrometry, chiroptical methods and NMR spectroscopy. J Pharm Biomed Anal. 2019;173:47-55. PubMed DOI
13. Zou P, Hou P, Low MY, Koh HL. Structural elucidation of a tadalafil analogue found as an adulterant of a herbal product. Food Addit Contam. 2006;23(5):446-51. PubMed DOI
14. Ulloa J, Sambrotta L, Redko F, et al. Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction. J Sex Med. 2015;12(1):152-7. PubMed DOI
15. Xia X, Song Z, He W, et al. Simultaneous determination of four PDE5 inhibitors and metabolites in rat plasma by UPLC-MS/MS. J Pharm Biomed Anal. 2025;262:116883. PubMed DOI